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FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0

Authors:
  • Amsterdam UMC

Abstract

The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about[18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out,interpret, and document quantitative FDG PET/CT examinations,but will concentrate on the optimisation of diagnostic quality and quantitative information.
GUIDELINES
FDG PET and PET/CT: EANM procedure guidelines
for tumour PET imaging: version 1.0
Ronald Boellaard &Mike J. ODoherty &Wolfgang A. Weber &Felix M. Mottaghy &
Markus N. Lonsdale &Sigrid G. Stroobants &Wim J. G. Oyen &Joerg Kotzerke &
Otto S. Hoekstra &Jan Pruim &Paul K. Marsden &Klaus Tatsch &
Corneline J. Hoekstra &Eric P. Visser &Bertjan Arends &Fred J. Verzijlbergen &
Josee M. Zijlstra &Emile F. I. Comans &Adriaan A. Lammertsma &Anne M. Paans &
Antoon T. Willemsen &Thomas Beyer &Andreas Bockisch &
Cornelia Schaefer-Prokop &Dominique Delbeke &Richard P. Baum &Arturo Chiti &
Bernd J. Krause
Published online: 14 November 2009
#The Author(s) 2009. This article is published with open access at Springerlink.com
Abstract The aim of this guideline is to provide a minimum
standard for the acquisition and interpretation of PET and
PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This
guideline will therefore address general information about
[18F]-fluorodeoxyglucose (FDG) positron emission
tomography-computed tomography (PET/CT) and is provid-
ed to help the physician and physicist to assist to carrying out,
interpret, and document quantitative FDG PET/CT examina-
tions, but will concentrate on the optimisation of diagnostic
quality and quantitative information.
Keywords Guideline .FDG .PET .PET/CT .Tumour .
Oncology .Quantification .QC .QA
Introduction
The aim of this guideline is to provide a minimum
standard for the acquisition and interpretation of PET
This guideline is a joint project of the EANM Oncology Committee
and the EANM Physics Committee. In addition, this guideline is based
on the following three documents:
(1) DGN (Deutsche Gesellschaft für Nuklearmedizin) Leitlinie:
FDG-PET/CT in der Onkologieby Krause BJ, Beyer T, Bockisch A,
Delbeke D, Kotzerke J, Minkov V, Reiser M, Willich N,
Arbeitsausschuss Positronenemissionstomographie der Deutschen
Gesellschaft für Nuklearmedizin. 2007.
(2) SNM Guidelines: Procedure Guidelines for tumour imaging
with 18F-FDG PET/CT 1.0.by Delbeke D, Coleman RE, Guiberteau
MF, Brown ML, Royal HD, Siegel BA, Townsend DW, Berland LL,
Parker JA, Hubner K, Stabin MG, Zubal G, Kachelries M, Cronin V,
Holbrook S. 2006.
(3) Applications of F18-FDG-PET in Oncology and Stand-
ardisation for Multi-Centre Studiesby Boellaard R, Oyen WJG,
Hoekstra CJ, Hoekstra OS, Visser EP, Willemsen AT, Arends AJ,
Verzijlbergen JF, Paans AM, Comans EFI, Lugtenburg E, Stoker J,
Schaefer-Prokop C, Zijlstra JM, Pruim J. HOVON Imaging work-
group and the Netherlands Society of Nuclear Medicine. 2007
R. Boellaard (*):O. S. Hoekstra :E. F. I. Comans :
A. A. Lammertsma
Department of Nuclear Medicine and PET Research,
VU University Medical Centre,
De Boelelaan 1117,
1081 HV Amsterdam, The Netherlands
e-mail: r.boellaard@vumc.nl
M. J. ODoherty :P. K. Marsden
PET Imaging Centre, Division of Imaging Sciences,
Kings College London and Guys and St Thomas
NHS Foundation Trust,
London, UK
W. A. Weber
Department of Nuclear Medicine, University Hospital Freiburg,
Freiburg, Germany
F. M. Mottaghy
Department of Nuclear Medicine,
University Hospital RWTH Aachen,
Aachen, Germany
M. N. Lonsdale
Department of Clinical Physiology and Nuclear Medicine,
Bispebjerg Hospital,
Copenhagen, Denmark
Eur J Nucl Med Mol Imaging (2010) 37:181200
DOI 10.1007/s00259-009-1297-4
and PET/CT scans with [
18
F]-fluorodeoxyglucose (FDG).
PET is a quantitative imaging technique and therefore
requires a common quality control (QC)/quality assurance
(QA) procedure to ensure that optimal images are acquired
for our patients and that these images would be acceptable
and interpretable by any clinician in another hospital. This
is essential for the management of patients who have the
right to have their health care provided in any hospital
they chose. Common standards will help promote the use
of PET/CT imaging and increase the value of publications
and their contribution to evidence-based medicine and
potentially enable the role of semi-quantitative and
quantitative image interpretation since the numeric values
should be consistent between platforms and institutes that
acquire the data. FDG PET/CT is being used increasingly
to evaluate tumour response in addition to diagnosis and
staging of tumours. Increasingly, research is being per-
formed in radiotherapy planning and it will be important
that areas such as edge detection of tumours have a
translatable measurement.
This guideline will therefore address general infor-
mation about [
18
F]-fluorodeoxyglucose (FDG) positron
emission tomography-computed tomography (PET/CT)
and is provided to help the physician and physicist to
assist in carrying out, interpret and document quantitative
FDG PET/CT examinations, but will concentrate on the
optimisation of diagnostic quality and quantitative infor-
mation. Note, that in this guideline quantification of FDG
PET and PET/CT is defined as quantification using
standardised uptake values (SUV), as it represents the
most commonly used (semi-)quantitative parameter for
analysis of oncology FDG PET studies. However, other
(full) quantitative measures, which require more complex
data-collection procedures, are being used as well, but
they are beyond the scope of the present guideline. In this
guideline, areas of information will provide a minimum
standard for FDG PET and PET/CT data acquisition,
quality control, and quality assurance.
The Procedure Guidelines for Tumour Imaging with
FDG PET/CT 1.0 of the Society of Nuclear Medicine
S. G. Stroobants
Department of Nuclear Medicine, University Hospital Antwerpen,
Antwerpen, Belgium
W. J. G. Oyen :E. P. Visser
Department of Nuclear Medicine,
Radboud University Nijmegen Medical Centre,
Nijmegen, The Netherlands
J. Kotzerke
Clinic and Outpatient Clinic for Nuclear Medicine,
University Hospital Dresden,
Dresden, Germany
J. Pruim :A. M. Paans :A. T. Willemsen
Department of Nuclear Medicine and Molecular Imaging,
University Medical Centre Groningen,
Groningen, The Netherlands
K. Tatsch
EANM Research Ltd. (EARL),
Vienna, Austria
C. J. Hoekstra
Department of Nuclear Medicine, Jeroen Bosch Hospital,
s-Hertogenbosch, The Netherlands
B. Arends
Department of Clinical Physics, Catharina Hospital,
Eindhoven, The Netherlands
F. J. Verzijlbergen
Department of Nuclear Medicine, St. Antonius Hospital,
Nieuwegein, The Netherlands
J. M. Zijlstra
Department of Haematology,
VU University Medical Centre,
Amsterdam, The Netherlands
T. Beyer
cmi-experts GmbH,
Zurich, Switzerland
A. Bockisch
Clinic for Nuclear Medicine,
University Hospital Essen,
Essen, Germany
C. Schaefer-Prokop
Department of Radiology, Academic Medical Center,
Amsterdam, The Netherlands
D. Delbeke
Department of Radiology and Radiological Sciences,
Vanderbilt University Medical Center,
Nashville, TN, USA
R. P. Baum
Department of Nuclear Medicine, Center for PET/CT,
Zentralklinik Bad Berka, Germany
A. Chiti
Nuclear Medicine, Istituto Clinico Humanitas,
Rozzano, MI, Italy
B. J. Krause
Department of Nuclear Medicine,
Technische Universität München,
Munich, Germany
182 Eur J Nucl Med Mol Imaging (2010) 37:181200
(SNM)
1
[1], the German Guidelines for FDG-PET/CT in
Oncology
2
[2], the quality control/assurance procedures
used in the UK for lymphoma/head and neck cancer studies
and the Netherlands protocol for standardisation of quan-
titative whole-body FDG PET/CT [3] studies have been
integrated in the present guideline. An overview of other
and previously published guidelines [1,2,414]or
recommendations can be found in the supplement issue of
the Journal of Nuclear Medicine 2009 [15].
Principle
Positron emission tomography (PET) is a tomographic
technique that computes the three-dimensional distribution
of radioactivity based on the annihilation photons that are
emitted by positron emitter labelled radiotracers. PET
allows non-invasive quantitative assessment of biochem-
ical and functional processes. The most commonly used
tracer at present is the glucose analogue FDG. FDG
accumulation in tissue is proportional to the amount of
glucose utilisation. Increased consumption of glucose is a
characteristic of most cancers and is in part related to
over-expression of the GLUT-1 glucose transporters and
increased hexokinase activity. Given the kinetics of FDG
adequate static images are most frequently acquired
approximately 60 min after administration. It is recog-
nized, however, that the uptake period is highly variable,
FDG concentration not reaching a plateau for up to 46
hinsometumours[16]. Moreover, not all cancers are
FDG avid. Variable uptake is likely related to biological
features of individual cancers, as is observed in broncho-
alveolar carcinomas, renal, thyroid cancers, several subtypes
of malignant lymphoma, carcinoids but also most prostate
carcinomas. The reason and prognostic relevance of this
biological heterogeneity is not always clear. However, in the
majority of cases, FDG PET is a sensitive imaging modality
for the detection, staging, re-staging as well as for assessment
of therapy response in oncology [6,1725].
In contrast to PET, computed tomography (CT) uses an
x-ray beam to generate tomographic images. CT allows the
visualisation of morphological and anatomic structures with
a high anatomical resolution. Anatomical and morpholog-
ical information derived from CT can be used to increase
the precision of localisation, extent, and characterisation of
lesions detected by FDG PET.
FDG PET and CT are established imaging modalities
that have been extensively validated in routine clinical
practice. Integrated PET/CT combines PET and CT in a
single imaging device and allows morphological and
functional imaging to be carried out in a single imaging
procedure. Integrated PET/CT has been shown to be
more accurate for lesion localisation and characterisation
than PET and CT alone or the results obtained from PET
and CT separately and interpreted side by side or
following software based fusion of the PET and CT
datasets. PET/CT gains more and more importance in
oncology imaging. At the same time, there is greater
awareness that the quantitative features of PET may have
a major impact in oncology trials and clinical practice.
Therefore this guideline focuses on the use of FDG PET/
CT in oncology.
Definitions
&An integrated PET/CT system is a combination of a
PET and a CT scanner with a single patient table.
&PET/CT allows a sequential acquisition of corresponding
PET and CT portions of the examination without having to
move the patient. Both data sets are intrinsically co-
registered given that the patient does not move during or in
between the acquisitions.
&The PET+CT fusion is the mechanical and data related
fusion of PET and CT volume data sets in a combined
data set. The software fusion of separate PET and CT
data sets is referred to as PET+CT.
&A fused PET+CT data set allows the combined visual-
isation of the fused PET and CT datasets.
&A PET/CT examination can include the whole body or a
portion of the body.
&Total body imaging: from the top of the head through
the feet (only in a minority of the cases).
&Whole-body imaging: Base of the skull-base to mid-
thigh imaging (covers most of the relevant portions of
the body in oncology imaging).
&Limited-area tumour imaging (for the evaluation of
tumour-related changes in a limited portion of the body).
&In PET/CT attenuation and scatter correction is carried
out using the CT-transmission data.
&Low-dose CT or anatomical CT: CT that is only
performed in order to carry out an attenuation correction
(CT-AC) or used for anatomical co-localisation of PET-
findings (with reduced voltage and current of the x-ray
1
Sections of this document were adapted and reprinted with permission
of the Society of Nuclear Medicine, Procedure Guidelines for Tumour
Imaging with 18F-FDG PET/CT: Delbeke D (chair), Coleman RE,
Guiberteau MJ, Brown ML, Royal HD, Siegel BA, Townsend DW,
Berland LL, Parker JA, Hubner K, Stabin MJ, Zubal G, Kachelreiss M,
Cronin V, Hoolbrook S. J Nucl Med 2006; 47: 885895
2
Sections of this document were translated and reprinted with permission
of the DGN (Deutsche Gesellschaft für Nuklearmedizin): Krause BJ,
Beyer T, Bockisch A, Delbeke D, Kotzerke J, Minkov V, Reiser M,
Willich N und der Arbeitsausschuss Positronen-Emissions-Tomographie
der Deutschen Gessellschaft für Nuklearmedizin. FDG-PET/CT in
oncology. German Guideline. Nuklearmedizin 2007; 46: 291301
Eur J Nucl Med Mol Imaging (2010) 37:181200 183
beam), i.e. a low-dose CT is NOT intended for
radiological diagnosis.
&If clinically indicated, a proper diagnosticCT scan
with intravenous and/or oral contrast media and deep
inspiration breath hold can typically be combined with
the PET/low-dose CT acquisition.
Indications
PET is a rapidly evolvingfield at both the national and
international level, with sometimes striking differences
between individual countries. The summary below is
therefore subjective in nature and based on a combination
of expert experience and scientific literature [6,17,18,20
26]. An excellent overview is given in [6], but these
indications are constantly changing and require updating
with time.
&Primary presentation: diagnosis: unknown primary
malignancy, differentiation of benign and malignant
lesions of e.g. a solitary lung nodule, especially in case
of discrepant clinical and radiological estimates of the
likelihood of cancer);
&Staging on presentation: non-small-cell lung cancer, T3
oesophageal cancer, Hodgkins disease, non-Hodgkins
lymphoma, locally advanced cervical cancer, ENT
tumours with risk factors and locally advanced breast
cancer.
&Response evaluation: malignant lymphoma, GIST, at
present other applications only in a research setting.
Application for oesophageal, colorectal, lung and breast
cancer appear promising.
&Restaging in the event of potentially curable relapse (for
FDG avid tumours)
&Establishing and localizing disease sites as a cause for
elevated serum markers (e.g. colorectal, thyroid, ovar-
ian, cervix, melanoma, breast and germcell tumours)
&Image guided biopsy (e.g. brain tumours) and radio-
therapy planning
Data that should accompany the request for a PET/CT
study
&Indication, reason for request of PET or PET/CT study
(see Indications)
&Height and body weight (these must be determined
precisely in the case of SUV measurements, see below).
With serial studies in the same patient, weight must be
measured directly prior to each PET study because body
weight often changes during course of disease.
&(If known) tumour type, tumour sites that have already
been noted
&Oncology prior history, relevant co-morbidity (especial-
ly inflammation)
&Diabetes mellitus (including medication)
&Results of other imaging tests (especially CT, MRI).
&In case of therapy evaluation: type and date of last
therapeutic intervention
&Allergy for contrast agents
&Renal function
Radiopharmaceutical
Product : [
18
F]-fluorodeoxyglucose (FDG)
Nuclide : Fluorine-18
Dosage : Dependent on the system and the patients
weight. (See Performing the PET/CT
study).
Administration : Intravenous
Synthesis and
Quality Control
: Conform the European Pharmacopeia
Patient preparation
The main purpose of the patient preparation is the reduction
of tracer uptake in normal tissue (kidneys, bladder, skeletal
muscle, myocardium, brown fat) while maintaining and
optimizing tracer uptake in the target structures (tumour
tissue). In the following, a generally applicable protocol is
outlined:
&Patients are not allowed to consume any food or sugar
for at least 6 h prior to the start of the PET study (i.e.
with respect to time of injection of FDG). In practice,
this means that patients scheduled to undergo the PET
study in the morning should not eat after midnight and
preferably have a light meal (no alcohol) during the
evening prior to the PET study. Those scheduled for an
afternoon PET study may have a light breakfast before
8.00 a.m. (i.e. up to two sandwiches, no sugars or sugar
containing sandwich filling). Medication can be taken
as prescribed.
&Adequate pre-hydration is important to ensure a
sufficiently low FDG concentration of FDG in urine
(less artefacts) and for radiation safety reasons (for
example, 1 l of water in the 2 h prior to injection; where
necessary, account for volume of water in oral contrast
medium for a diagnostic CT scan).
184 Eur J Nucl Med Mol Imaging (2010) 37:181200
&Parental nutrition and intravenous fluids containing
glucose should be discontinued at least 4 h before the
PET/CT examination. In addition, the infusion used to
administer intravenous pre-hydration must not contain
any glucose.
&During the injection of FDG and the subsequent uptake
phase the patient should remain seated or recumbent
and silent to minimise FDG uptake in muscles. For a
brain examination with FDG, injection should take
place in a darkened and quiet room and the patient
should stay there for the subsequent uptake phase to
avoid areas of enhanced uptake due to brain activation.
The patient should be kept warm starting at 3060 min
before the injection of FDG and throughout the
following uptake period and PET examination to
minimise FDG accumulation in the brown fat (espe-
cially relevant if the room is air conditioned). Moreover,
all patients must avoid (extreme) exercise for at least
6 h before the PET study (for example, they must not
cycle to the hospital).
&In case of pregnancy: see the Society of Nuclear
Medicine Procedure Guidelines for General Imaging
Version 3 or national guidelines.
The following recommendations apply to patients with
diabetes mellitus:
type II diabetes mellitus (controlled by oral medication)
the PET study should preferably be performed in the
late morning
patients must comply with the fasting rules indicated above
patients continue to take oral medication to control
their blood sugar.
type I diabetes mellitus and insulin-dependent type II
diabetes mellitus
ideally, an attempt should be made to achieve normal
glycaemic values prior to the PET study, in consultation
with the patient and his/her attending medical doctor
the PET study should be scheduled for late morning
the patient should eat a normal breakfast at 7.00 a.m. and
inject the normal amount of insulin. Thereafter the patient
should not consume any more food or fluids, apart from
the prescribed amount of water.
It is good practice to check the blood glucose level of the
patient on arrival at the imaging centre to ensure the
patientssugar is not too low or high, since this may obviate
an unnecessary wait.
In the case of patients on continuous insulin infusion, the
PET study should if possible be scheduled early in the
morning. The insulin pump is kept on the night setting
until after the PET study. The patient can have breakfast
after the PET study.
Extra notes
&A transurethral catheter is placed only if required (expected
urinary activity prohibiting appropriate image interpreta-
tion), and this should preferably be done before FDG is
administered. Administration of a diuretic (furosemide)
can be considered in the case of small pelvic tumours, but it
is not necessary to use this routinely. Clinical experience
suggests that proper prehydration avoids most potential
reading errors and that delayed imaging or furosemide
intervention is very rarely necessary
&There is no reason for routine administration of
sedatives (e.g. short-acting benzodiazepines). Sedatives
can be considered in the case of tumours in the head
and neck region to reduce muscle uptake or in anxious
claustrophobic patients. In the case of children, sedation
may be required depending on the age or the tumour
type. A number of agents have been tried and are being
tested (e.g. beta-blockers) to reduce brown fat uptake. If
an agent is to be used as part of a clinical trial it needs
to be effective and must not affect tumour uptake of the
radiopharmaceutical. Patients should be instructed not
to drive a car after sedation.
&Blood glucose level must be measured prior to
administering FDG. A Glucometer or a similar bedside
device (capable of performing overall euglycaemia
measurements) can be used for this purpose, but a
blood glucose test must be performed with a calibrated
and validated method if plasma glucose level is used as
correction of SUV measurements [27]:
If plasma glucose level is <7 mmol/l (or <120 mg/dl)
the FDG PET study can be performed
If plasma glucose level is 7 mmol/l (or >120 mg/dl)
the FDG PET study must be rescheduled or the
patient excluded depending on the patient circum-
stances and the trial being conducted.
In case the study cannot be rescheduled or when
elevated glucose levels cannot be ruled out, blood
glucose levels must always be measured using a
calibrated and validated method and SUV must be
reported with and without glucose correction. Note
that specifically in response-assessment studies
blood glucose levels may change with the therapy
and it is strongly recommended to measure blood
glucose levels using validated and calibrated meth-
ods (no bedside devices) during all sequential PET
examinations.
Reduction of the blood glucose level by administra-
tion of insulin can be considered, but the PET/CT
examination should also be postponed depending on
the type and route of the administration of insulin.
N.B.: insulin must not be given to reduce glucose
Eur J Nucl Med Mol Imaging (2010) 37:181200 185
levels (this leads to greater muscle uptake of FDG)
unless the interval between administration of insulin
and administration of FDG is more than 4 h.
&When diagnostic contrast-enhanced CT with intravenous
contrast media is to be performed (after the PET/CT
examination), indications, contraindications and restric-
tions have to be assessed by a qualified physician/
radiologist. Medication that interacts with intravenous
contrast (e.g. metformin for the treatment of diabetes) and
relevant medical history (e.g. compromised renal func-
tion) have to be taken into consideration.
&For CT of the abdomen or pelvis, an intraluminal
gastrointestinal contrast agent may be administered to
improve the visualisation of the gastrointestinal tract in
CT (unless it is not necessary for the clinical indication
or it is medically contraindicated). Contrast agents must
only be used in accordance with the recommendations
given in paragraph Other acquisition parameters,CT-
protocol.
Essential data/aspects and required materials
for the FDG PET study
Required materials
&(Ideally) a triple-channel system (=standard system with
three-way tap to enable saline flush) for administering
the tracer and flushing with physiological saline.
However, if automated bedside administration systems
are being used then other types of lines may be required
to obtain the same flushing and administration results.
&Bedside glucose meter, to check serum glucose,
especially in patients susceptible to hyperglycaemia
(diabetics, patients taking corticosteroids). Note that
many (other) bedside methods do not have sufficient
precision to be used for SUV correction [27].
&Weighing scales that are accredited and checked at least
annually.
Clinical information required for scan procedure
and interpretation
&Before the PET/CT examination the following clinical
data should be available: a history focused on the patients
disease and localisation of disease, date of diagnosis, type
of verification of diagnosis (biopsy results, time of biopsy,
histopathological report) and prior therapies (surgery,
radiation therapy, chemotherapy, administration of bone
marrow stimulants and steroids), current medication and
previous imaging results
&Relevant comorbidity: diabetes, concurrent inflamma-
tory disease.
&Prior therapy: nature and timing of last relevant surgery,
radiation, chemotherapy, bone marrow stimulants and
steroids. In clinical trials, the study protocol should
define the interval between administration of such
substances and the PET study. For clinical practice
several recommendations have been published [7] (see
also e.g. JNM Supplement 2009). A minimum interval
between the last dose (chemotherapy) and the PET
study should be 10 days, if possible, or probably as
close to the next treatment administration as possible.
&Date at which results of the PET or PET/CT study must
be available.
&Ability of the patient to lie still in the PET or PET/CT
system for the duration of the examination (2045 min)
&History of claustrophobia
&Ability to put his/her arms over the head
Precautions
See Society of Nuclear Medicine Procedure Guidelines
for General Imaging Version 3
Radiation exposure
&The radiation dose with PET/CT or PET is the
combination of the radiation exposure caused by the
radiopharmaceutical and the CT study (or the external
transmission sources). Radiation dose of diagnostic
CT has been a matter of debate over the last years,
particularly for paediatric examinations. It is difficult
to state a mean dose for a CT scan because of the
variety of applications, protocols, and CT systems.
Especially for children but also for adults it is of
importance to optimise the radiation exposure with
respect to the diagnostic question. In recent
years there has been much effort to minimise the
radiation dose related to a conventional CT-or PET-
examination.
&The radiation dose of FDG is approximately
2×10
2
mSv/MBq according to ICRP publication
106 [28], i.e. about 34 mSv for an administered
activity of 185 MBq. The radiation exposure related to
a CT performing a PET/CT examination depends on the
intention of the CT carried out and may differ from case
to case: the CT can be performed as a low-dose CT
(with lower voltage and current) to be used for
attenuation correction and localisation of PET lesions.
Alternatively (or additionally) a diagnostic CT can be
indicated (in most cases with intravenous contrast agent
application and deep inspiration in case of a chest CT)
186 Eur J Nucl Med Mol Imaging (2010) 37:181200
for a full diagnostic CT examination. The effective CT-
dose could range from 120 mSv and may be even
higher for a high resolution diagnostic CT scan. Given
the variety of CT systems and protocols the radiation
exposure for a PET/CT examination should be estimat-
ed specific to the system and protocol being used and
an expert from radiology or guidelines provided by the
European radiological societies should be consulted
regarding effective dose from the CT examination.
3
&The choice of the imaging protocol used strongly
depends on the clinical question and must be discussed
for every single case. In this respect, special attention is
required in case of paediatric applications. For the
optimisation of PET/CT examinations, dose reduction
techniques should be considered.
Performing the PET/CT study
Preparation and execution
&In case of manual administration:
An indwelling intravenous device is used to
administer the FDG intravenously once the
patients blood glucose has been determined and
blood samples for laboratory testing have been
taken if necessary. Make sure that if there is a
needle on the syringe it is free from FDG.
Flush and rinse out the administration syringe with
at least 10 ml of normal saline (NaCl 0.9%) using
the three-way valve.
&In case of automated administration:
Make sure that the automated system and proce-
dures assures a net administered FDG activity
within 3% accuracy (this must be ensured by
manufacturer and verified by the user), i.e. the
actual administered activity may not deviate more
than 3% from that indicated by the reading of that
device or used dose calibrator. Follow instructions
given by the manufacturer.
&The administration system can be removed after intrave-
nous administration (unless CT contrast agent is to be
administered subsequently by intravenous injection).
&The ambient conditions in the waiting room must be
relaxing and warm. Give the patient extra blankets if
necessary.
&Tell the patients to lie or sit as calmly as they can, and
not to talk. Provide comfortable beds or chairs. They
may go to the toilet while waiting, preferably after the
first 30 min p.i. Ask the patient to use the bathroom 5
min before the start of the PET study.
&An intense bladder or ureter activity concentration can
impair the interpretation of lesions in the pelvis and
retroperitonium. Hydration and loop diuretics (e.g.
furosemide i.v.) may be used to reduce bladder activity
and radiation exposure to the bladder. Therefore, during
the waiting period, patients will be asked to drink
another half a litre of water, or this amount can be
given in the form of physiological saline intravenous-
ly, if such fluid load is not medically contra-indicated.
This is of course dependent on the patients other
clinical conditions, e.g. impaired renal function or
poor cardiac function, where this amount of fluid may
be contraindicated.
&The recommended interval between FDG administra-
tion and the start of acquisition is 60 min. However, for
certain clinical trials this may change depending on the
disease and aims of the study. This should then be
clearly stated in the study protocol. The actual interval
should be recorded, i.e. the time of FDG injection
(administration) should be reported. Please be aware
that this is usually not equal to the FDG activity assay
or calibration time. Note that consistency of SUV
measurements (in-house and compared with literature)
depends on strict application of the interval schedule
and therefore a 60-min interval is recommended. When
repeating a scan on the same patient, especially in the
context of therapy response assessment,itisessential to
apply the same interval (tolerance ±5 min). In addition,
use of the same PET or PET/CT system and identical
acquisition and reconstruction settings must be applied
when making multiple scans of the same patient.
&Scan trajectory: for most oncology indications, a whole-
body scan is sufficient. A whole-bodyuptake normal-
ly covers the part of the body from the mid-femora to
the external auditory meatus (in that direction, as
bladder activity increases during the scan). A longer
scanning trajectory may be used if appropriate. Whole-
body PET/CT offers the opportunity for whole-body
staging/re-staging. For most oncology indications, skull
base-to-mid thigh tumour imaging is sufficient. Extend-
ed whole-body examinations are performed in tumours
that show a high probability of metastases in the head,
skull, brain, cranium, and in the lower extremity.
Limited-area tumour imaging can be considered for
follow-up examinations, if the disease is restricted to a
3
It should be noted that the entity effective dosedoes not
necessarily reflect the radiation risk associated with this nuclear
medicine examination. The effective dose values given in this
guideline are used to compare the exposure due to different medical
procedures. If the risk associated with this procedure is to be assessed,
it is mandatory to adjust the radiation-associated risk factors at least
according to the gender and age distribution of the institutions patient
population.
Eur J Nucl Med Mol Imaging (2010) 37:181200 187
defined region (i.e. solitary pulmonary nodule, suspi-
cion of lung cancer, examination of hilar lymph nodes,
head and neck tumours, assessment of therapy
response).
&The patient should be positioned with the arm elevated
over the head to avoid beam hardening artefacts as well
as artefacts caused by truncation of the field of view.
For the examination of head and neck tumours, a two-
step protocol is recommended (head and neck portion
and from the apex of the lung through mid thigh) with
the appropriate acquisition and reconstruction parame-
ters adapted for the protocol. Alternatively, the arms can
be positioned along the side for head and neck imaging.
If the FDG PET/CT data are used for radiation
planning, the examination should be carried out in the
radiation position using the same dedicated radio-
opaque positioning devices as used in the radiotherapy
department (e.g. same table tops, laser alignment,
immobilisation measures, etc.).
&Scan acquisition depends on various factors, including
the system type and acquisition mode (2D, 3D). For CT
settings in case of PET/CT, CT whole-body or low-dose
CT, see Other acquisition parameters, CT-protocol.
Transmission scanning time for each bed position
depends on whether the scan is a CT scan or a
transmission scan with Ge-68/Ga-68 source.
&In general, PET/CT is carried out using a protocol
comprising a scanogram/scout scan/topogram and a
low-dose CT for attenuation correction (CT-AC) and
anatomical correlation. IV contrast agent must not be
administered during the low-dose CT, used for attenu-
ation correction purposes, because of its potential
influence on SUV calculation.
&In the case of single slice or dual-slice CT, artefacts are
created in the diaphragm area when the patient breathes.
The patient must therefore hold his/her breath for a few
seconds on the technicians instructions during CT-AC
acquisitions. No such instructions need be given in the
case of PET/CT systems with more than two slices. The
CT-AC scan can then be carried out while the patient
continues to breath shallowly.
&A standard diagnostic CT scan with (i.v.) contrast agent
may, if appropriate, be carried out according to standard
radiological methods after the low-dose CT and PET
acquisition in case quantification of the PET study will
be performed or is required.
&Recommendations for FDG activities are based on
assuming a fixed scan duration of 5 min per bed position
and a bed overlap of less than 25%. In the case of 2D
scans: ca. 5 MBq/kg body weight (±10%). In the case of
3D scans: ca. 2.5 MBq/kg body weight (±10%). In
paragraph Permitted protocol alterations regarding FDG
activity detailed recommendations and permitted alter-
ations of the administration protocol are given, including
those for systems that apply a 50% bed overlap.
&For children (<19 years), FDG activity must conform to
the EANM recommendations given in the EANM
paediatric dosage card [29].
&Specifications of transmission scans based on a Ge-68
line source: >2 min per bed position. In paragraph
Other acquisition parameters, CT-protocol, recom-
mendations are given for the CT-AC.
Permitted protocol alterations regarding FDG activity
When using systems with a high count rate capability
(LSO, LYSO, and GSO-based cameras with or without time
of flight), the administered FDG activity and scan duration
for each bed position must be adjusted so that the product
of the FDG activity and scan duration +10% is equal to or
greater than the specifications set out below. Therefore, one
may decide to apply a higher activity and reduce the
duration of the scan or, preferably, use reduced activity and
increase scan duration, thereby keeping ALARA principles
in mind as well.
&The figures for systems with bed overlap of<25% are:
Product of MBq/kg × min/bed>27.5 for 2D scans
Product of MBq/kg × min/bed> 13.8 for 3D scans.
The dosage is then calculated as follows:
FDG activity in MBq for 2D scans=27.5 × weight/
(min/bed)
FDG activity in MBq for 3D scans=13.8 × weight/
(min/bed)
&And for systems with a bed overlap of 50%:
Product of MBq/kg × min/bed>6.9 (3D only)
FDG activity in MBq=6.9 × weight/(min/bed)
&The specifications indicate that heavier patients receive
a higher FDG activity. A short scanning duration per
bed position should also be offset by a higher FDG
activity [3,30]. Two model calculations are given in
Appendix Ito clarify the situation.
&For obese subjects (>90 kg), increase of scanning time
(time per bed position) rather than increase of FDG
activity is recommended to improve image quality. A
recent publication suggests that FDG activities higher
than 529 MBq for patients above 90 kg should not be
applied for LSO systems [31]. Therefore, it is recom-
mended to keep administered activity below 530 MBq.
&A maximum allowed FDG activity may be imposed by
national law. In the latter case, increase of scanning time
should be applied to keep FDG activity within legal limits.
&If the scanning duration for each bed position can be set
separately, then the scanning duration per bed position
188 Eur J Nucl Med Mol Imaging (2010) 37:181200
may be further reduced by up to 50% for bed positions
outside the thorax and abdomen (i.e. at the level of the
head, neck and legs, as attenuation is less). The FDG
activity must still be calculated assuming the scanning
duration per bed position as used for bed positions at
the level of the thorax and the abdomen.
&In all cases the administered activity should not result in
count rates above the count rate capability of the PET or
PET/CT system being used. Increase of scan duration
should then be applied to improve image quality.
Other acquisition parameters
Emission scans:
&Online randoms correction should be based on delayed
coincidence time windowtechnique or randoms cor-
rection using a model based on (block) singles count
rates
&Indication of the correct isotope, the patients height and
body weight, and the FDG activity administered. Please
also note and report assay activity (=FDG activity) and
assay time (=activity calibration time). In addition,
indicate time of injection (usually not equal to assay
time or activity calibration time) should be noted and
reported.
&Decaycorrectionmustbeon(see also Image
reconstruction).
CT-protocol
&The CT in the framework of a PET/CT examination
comprises the topogram and the helical CT scan.
&If a CT is solely performed for attenuation and scatter
correction and co-localisation, the acquisition parame-
ters (tube current, voltage, slice thickness, rotation time,
and pitch) should be selected in order to minimise the
radiation exposure for the patient.
&For a diagnostic contrast-enhanced CT, standard CT
milliampere-seconds settings or those given by
the radiological societies/radiologist should be used.
The modulation of the tube current can be used to
lower the radiation exposure of the patient. Depending
on the clinical question, intravenous and/or oral contrast
agents may be used. It might be useful to perform a
diagnostic CT only for portions of the body, whereas for
the rest of the body a low-dose CT is performed for
attenuation correction and co-localisation. High intra-
venous concentrations of contrast material may cause
artefacts on the reconstructed PET image and affect
quantification and should thus not be applied during the
CT-AC in case quantification (i.e. SUV) is performed
(but may be used after concluding the PET/CT
examination during an additional diagnostic CT). In
case of PET/CT scans without need for quantification,
intravenous contrast agents may be used directly (i.e.
this CT may also be used for attenuation correction
purposes) during the PET/CT study because the impact
on visual image quality and interpretation is modest.
However, deep inspiration at chest CT will obviously
cause misregistration and artifacts if low-dose CT (with
normal breathing) is replaced by such a diagnostic deep
inspiration CT.
&Oral contrast agents allow a better delineation of the
gastrointestinal tract. Positive contrast material (like
diluted barium) as well as negative contrast material
(for example water) can be used. High intraluminal
concentrations of barium or iodinated contrast agents
can cause an attenuation correction related artefact in
the PET images resulting in an overestimation of FDG
accumulation at those sites. These artefacts can be
avoided by using negative contrast agents. However,
administration of water only as negative intraluminal
contrast agent itself is associated with a fast resorption
and can cause increased nonspecific FDG accumulation
in the bowel. In case quantification of the PET/CT
studies is required, it is recommended to use diluted
positive contrast agents only. The concentration of
diluted positive contrast agents should be low enough
to guarantee absence of attenuation correction artefacts,
which should be verified for each combination of PET/
CT system, PET/CT image reconstruction software and
contrast agent being used.
&Ensure that the patient is lying within the CT-AC field
of view (FOV) and in the same position as during
emission scanning.
Pitfalls
&In some PET/CT systems, the FOV of the CT and CT-
AC is smaller than that of the PET. Truncating the CT
(and CT-AC) causes reconstruction artefacts and there-
fore inaccurate quantification of the PET scan. When
available, truncation corrections algorithms may be
applied during image reconstruction (and/or during
processing of CT used for attenuation correction).
However, one needs to demonstrate that quantification
is not affected by CT truncation even when truncation
corrections are applied. As the amount of truncation
may vary across scans and subjects, it will be difficult
to ensure proper quantification across scans and
subjects. It is therefore strongly recommended to avoid
any CT truncation. It should be noted that CT
Eur J Nucl Med Mol Imaging (2010) 37:181200 189
truncation may occasionally seriously affect the scatter
correction and may lead to non-quantitative results.
&When using Ge-68 transmission sources, they must be
replaced on time (i.e.,: at least once every 18 months)
and/or following the manufacturers recommendations.
It is recommended to compensate for the decay of
transmission scan sources over time by increasing
transmission scan durations, e.g. by performing trans-
mission scans based on total number of collected
counts, if possible [32].
&Make sure that all clocks (of dose calibrator and PET or
PET/CT system) are synchronized. Consult your local
service engineer when needed. Clocks should be
synchronised with the official local time within 1 min
(in case of FDG studies).
Image reconstruction
PET image reconstruction
The PET emission data must be corrected for geometrical
response and detector efficiency (normalisation), system dead
time, random coincidences, scatter, and attenuation. Some of
these corrections (for example attenuation correction) can be
directly implemented in the reconstruction process. In all
cases, all corrections needed to obtain quantitative image data
should be applied during the reconstruction process. Data
acquired in the 3D mode can be reconstructed directly using a
3D-reconstruction algorithm or rebinned in 2D data and
subsequently be reconstructed with a 2D-reconstruction
algorithm. Iterative reconstruction algorithms represent the
current standard for clinical routine and have meanwhile
replaced filtered backprojection algorithms for PET recon-
struction. It is good clinical practice to perform reconstruc-
tions with and without attenuation correction to tackle
potential reconstruction artefacts caused by a CT-based
attenuation correction. For clinical cases, reading the recon-
structed 3D volume data set is visualized in transaxial,
coronal, and sagittal slices, but also the maximum intensity
projections should be available.
Further standardisation of reconstruction settings is
necessary in order to obtain comparable resolutions and
SUV recoveries and make SUVs interchangeable, i.e.
reconstructions are chosen such to achieve convergence
and resolution matching across various PET and PET/CT
systems and sites, especially within a multi-centre setting
[15,30,33]. However, also for clinical practice, strict
standardisation is needed to provide the same quality of care
across sites and to allow for exchange and use of quantitative
PET information elsewhere. Some indicative reconstruction
settings are suggested in Appendix II. However, most
importantly, reconstructions should be chosen so that they
meet the multi-centre QC specifications for both calibration
QC and image quality/SUV recovery QC, as described in
Quality control and inter-institution cross-calibration.
Exceptions/special features
Various new types of cameras are coming into the market. It is
not yet possible to specify rational dosage, acquisition, and
reconstruction specifications for them. Moreover, default
reconstruction settings may change over time. Therefore,
institutions may deviate from the recommended/prescribed
dosage and acquisition protocol if it can be demonstrated that
the alternative protocol provides equivalent data. The conver-
gence and overall final image resolution must also match this
study protocol QC specification. Compliance with these
requirements must be demonstrated by means of the tests
described under Quality Control and inter-institution cross-
calibration in Quality control and inter-institution cross-
calibration. Calibration and activity recovery coefficients
may not deviate from multi-centre standard specifications by
more than 10%. These specifications are given in Quality
control and inter-institution cross-calibration. In other
words: any combination of acquisition and reconstruction
protocol and/or settings which meets the multi-centre QC
specifications given later and especially those for the
(absolute) activity (or SUV) recovery coefficients is allowed.
CT image reconstruction
The CT data that are acquired during the PET/CT scanning
session are usually reconstructed by use of filtered back
projection or a similar algorithm. Depending on the CT-
protocol and the diagnostic question separate CT recon-
structions for the PET attenuation correction and for the
diagnostic CT are performed. The reconstructions differ in
their slice thickness, slice overlap, filter, etc. In addition to
the reconstruction kernel that modulates the image charac-
teristics within the slices (i.e. spatial resolution, edge
enhancement and noise texture), a longitudinal filter in the
z-dimension is used to optimise the resolution in the z-
direction and to modify the slice-sensitivity profiles. The
measured attenuation values are normalized to the density
of water in order to assign a device-independent numeric
value in the framework of the reconstruction.
CT value ¼HU ¼1000 mmwaterðÞ
mwater
This procedure additionally reduces the dependency of the
attenuation values from the radiation energy. In modern CT-
tomographs, the spatial resolution in the z-dimension is almost
as high as the transaxial resolution and almost isotropic
190 Eur J Nucl Med Mol Imaging (2010) 37:181200
allowing image visualisation in coronal and sagittal views in a
high quality. Additionally, post-processing like volume
rendering or maximum intensity projections (MIPs) benefit
from the high quality of the raw data.
Reporting
Reporting PET findings and SUV calculations
The reconstructed PET and CT images are assessed from a
computer screen. The software packages for current PET/
CT systems enable visualisation of PET, CT, and PET+CT
fusion images in the axial, coronal, and sagittal planes as
well as maximum intensity projections in a 3D cine mode.
FDG PET images can be displayed with and without
attenuation correction. On all slices (of the attenuation
corrected data) quantitative information with respect to size
and FDG uptake can be derived. Images must be evaluated
using software and monitors approved for clinical use in
radiology and nuclear medicine. Characteristics of monitor
and settings should be in line with published standards (e.g.
the Medical Electrical Safety Standards (IEC 60601-1/EN
60601-1), the Medical ECM Standards (IEC 60601-1-2, EN
60601-1-2) or national guidelines). Moreover, environment
conditions (background light) must be at appropriate levels
to ensure adequate image inspection.
The presence or absence of abnormal FDG accumulation
in the PET images, especially focal accumulation, in
combination with their size and intensity are evaluated.
Absence of such accumulation is particularly significant if
other tests have revealed findings such as anatomical
abnormalities. Where necessary, the report correlates these
findings to other diagnostic tests and interprets them in that
context (in consultation with a radiologist where necessary)
and considers them in relation to the clinical data. For
response assessment, the images should be viewed over the
same dynamic grey scale or colour scale range, i.e. a fixed
colour scale e.g. from SUV=0 to 10 is recommended.
Both uncorrected and attenuation-corrected images need
to be assessed in order to identify any artefacts caused by
contrast agents, metal implants and/or patient motion.
Criteria for visual analysis must be defined for each
study protocol.
Standardized uptake values are increasingly used in
clinical studies in addition to visual assessments. SUV
is a measurement of the uptake in a tumour normalized
on the basis of a distribution volume. It is calculated as
follows:
SUV ¼Actvoi kBq=mlðÞ
Actadministered MBqðÞ=BW kgðÞ
The following calculation is applied in the case of
plasma glucose correction
SUVglu ¼Actvoi kBq=mlðÞ
Actadministered MBqðÞ=BW kgðÞ
Glucplasma mmol=lðÞ
5:0 mmol=lðÞ
In these calculations, Act
voi
is the activity measured in the
volume of interest (see Definitions for volumes of interest
(VOI) and regions of interest (ROI)), Act
administered
is the
administered activity corrected for the physical decay of FDG
to the start of acquisition, and BW is body weight. Patient
height, weight, and gender should be reported to allow for
other SUV normalisations (LBM, BSA). The latter is of
importance to meet EORTC recommendations [13] and, for
response assessment studies, when large changes in body
weight occur during the course of the treatment. As stated
earlier, it is recommended to measure plasma glucose levels
using validated methodology and calculate SUV with and
without plasma glucose correction in all response monitoring
assessment studies (Patient preparation,extranotes).Note
that the measured glucose content (Gluc
plasma
)isnormalised
for an overall population average of 5.0 mmol/l so that the
SUVs with (SUV
glu
) and without (SUV) correction of glucose
content are numerically practically identical (on average) [3].
Interpretation and pitfalls
Interpretation criteria
&A physiological and variable FDG accumulation can be
observed to a certain degree in most viable tissue: brain,
myocardium (in which the FDG accumulation can be
high in the fasting state), breast, liver, spleen, stomach,
intestine, kidneys, urine, skeletal muscle, lymphatic
tissue, bone marrow, salivary glands, thymus, uterus,
ovaries, testicles, and brown fat.
&In whole-body PET/CT examinations the brain shows a
high FDG accumulation. For the detection of brain
metastases FDG PET is therefore only of limited value.
In consequence FDG PET is usually not used for the
primary detection or exclusion of brain metastases.
&An increased FDG uptake is observed in neoplastic
lesions, granulation tissue (e.g. wound healing), infec-
tions and other inflammatory processes.
&Patterns of FDG uptake, established CT-morphological
criteria as well as correlation with patient history,
physical examination and other imaging modalities
may be helpful for the differentiation between malig-
nant and benign lesions. Semi-quantitative parameters
(for example SUV) gain increasing importance for
Eur J Nucl Med Mol Imaging (2010) 37:181200 191
therapy response monitoring and for assessing the
prognosis of patients.
&Detection limits obviously depend on the degree of
contrast between the tumour and its immediate sur-
roundings. Sensitivity of FDG PET is much lower in
diabetic patients. There is no single detection limit for
FDG PET since it depends on many factors. The most
significant of these are: histology (FDG avidity of the
type of tumour), the volume of vital tumour cells,
movement during acquisition (e.g. blurred signals in the
case of pulmonary foci), and physiological uptake in the
adjacent background. Although it is impossible to give
universal rules for detection limits, it has been demon-
strated that even in the case of tumours that take up
FDG in large amounts, such as melanoma, the sensitiv-
ity of FDG PET declines when the diameter of the
tumour is less than 6 mm. Non-specific, non-
physiological uptake is based on inflammatory processes
or uptake in brown fat (neck, upper mediastinum, para-
vertebral region). In patients who have undergone surgery,
uptake therefore depends on the extent of surgery and how
far the wound has healed: for example, there are few
visible signs of a mediastinoscopy after ten days but a
sternotomy will remain visible for months. The resolution
of FDG PET for bone fractures is more or less the same as
has been established for skeletal scintigraphy.
Additional remarks
&Though there are no conclusive data on the optimum
interval between chemotherapy and PET, an interval of
at least 10 days is generally considered between the last
treatment and PET. This is because of any possible
effects on tumour metabolism (such as macrophage
impairment) and systemic effects (such as bone marrow
activation following bone marrow depression, which
may or may not be caused by growth factors). The
effects of growth factors (Gm-CSF) or FDG biodistri-
bution (due to enhanced bone marrow uptake) do not
last for more than 2 weeks after the final administration.
It is assumed that the effects of radiotherapy are
somewhat longer lasting; investigation of cases of
laryngeal carcinoma treated by radiation has shown that
due to radiation-induced inflammation, it is best to wait
for about 3 months after the end of treatment before
conducting FDG PET. This timing fits well into this
clinical context as these patients rarely develop clinical
problems in the first 3 months after treatment.
&FDG PET is generally assessed using visual criteria (in
the context of oncology, looking for a focally increased
uptake that may be compatible with malignancy in the
clinical context. It is unclear how far semi-quantitative
measurements such as SUV can contribute to the
assessment, partly because of the considerable variability
in the methodology used [30,33]. This recommendation
is an attempt to increase uniformity of FDG PET
investigations in multi-centre studies and for routine
clinical applications. It is therefore also essential that the
equipment used is comparable. This can be achieved by
means of (cross-) calibration, as described in Quality
control and inter-institution cross-calibration.
Documentation and report
&Examination label
&Clinical information:
Indication for PET/CT-examination
Relevant patient history
Information relevant for reimbursement
&PET/CT-Examination and imaging protocol
Radiopharmaceutical with applied activity, purity,
injection type and site (localisation of injection),
time of injection, uptake time, body weight (for
each longitudinal study) and height, gender
Information concerning medication administered as
preparation of the PET scan
Field of view and patient positioning: whole-body
PET/CT, skull base to mid thigh, limited area and
position of the arms
Blood glucose level before the examination and
used methodology to obtain blood glucose
CT-protocol: low-dose or/and diagnostic CT, contrast
agent application (oral, intravenous, information on
concentrations and volumes, native, arterial, portal-
venous), scanned portion of the body
&Clinical report
Quality of the PET/CT-examination: i.e. limited due
to motion artefacts, FDG accumulation in muscles
and/or brown fat, hyperglycemia, CT-related arte-
facts, high patient body weight
Description of the localisation, the extent and the
intensity of pathological FDG accumulations relat-
ed to normal tissue. Description of relevant findings
in CT and their relation to pathological FDG
accumulations. FDG accumulation should be
reported as mild, moderate, or intense and com-
pared to the background uptake in e.g. the liver
parenchyma (mean SUV: 2.03.0; maximum SUV:
3.04.0). However, criteria for visual interpretation
must be defined for each study protocol and/or type
of cancer because they may differ for different
tumour locations and types. Some criteria have
192 Eur J Nucl Med Mol Imaging (2010) 37:181200
already been proposed [7,34]. The CT part of the
PET/CT report must described all findings (even in
the case they are PET negative), and exception being
that the CT is only used for attenuation correction.
&Limitations: If necessary, confounding factors influenc-
ing sensitivity and specificity of the PET/CT examina-
tion should be noted: small lesions (partial volume
effect), inflammatory changes, muscle activity, high
blood glucose levels at the time of injection
&Clinical context: Addressing the findings with respect to
the clinical questions asked in the context of the PET/
CT examination
&Complementary information: Comparison with previous
examinations should be part of the PET/CT report. PET/
CT examinations are more valuable, if they are
interpreted in the context of results of other imaging
examinations (for example CT, PET, PET/CT, MRI,
etc.) and relevant clinical data. If a PET/CT examination
is performed in the context of the assessment of
response to a therapy the extent and the intensity of
the FDG uptake should be documented. The European
Organisation for Research and Treatment of Cancer
(EORTC) has published criteria for the assessment of
therapy response with FDG as metabolic marker. The
documentation of a change in intensity of the FDG
accumulation with semi-quantitative parameters
expressed as absolute or relative changecan be used
for dedicated clinical questions. At present, relative
changes in SUV under therapy represent the most robust
parameter. A focus must be put on the equivalence of
the results achieved with respect to comparability of
technical protocols and data analysis.
&Summary and diagnosis
If possible, a definite diagnosis should be stated
whenever possible. Alternatively, an estimate of the
probability of a diagnosis should be given.
If relevant, differential diagnoses should be discussed
If appropriate, repeat examinations and/or addition-
al examinations should be recommended to clarify
or confirm findings.
For further reading, also see the Society of Nuclear
Medicine Procedure Guidelines for General Imaging.
Definitions for volumes of interest (VOI) and regions
of interest (ROI)
Definition:
&The maximum SUV measure (SUV
max
) is required for
each lesion as specified in the study protocol and/or as
considered clinically relevant. The voxel with maxi-
mum uptake should be determined as follows:
This volume of interest equals the voxel with
highest uptake in tumour/lesion. The maximum
uptake should be defined on original reconstructed
PET images, i.e. no additional rebinning, resam-
pling, smoothing by the user is allowed.
&Use of a 2D peak ROI/VOI is recommended as well
(providing SUV
peak
). The volume of interest that should
be generated is:
Approximately 1.2 cm diameter fixed size circular ROI
(defined in axial plane), centreed on the tumour area
with highest uptake, as recently suggested in [12].
&Use of a 3D peak ROI/VOI (providing SUV
3Dpeak
) may
be determined (when possible) as follows:
3D 1.2 cm diameter spherical VOI centred on area with
maximum uptake (SUV
3Dpeak
)may be defined [12].
&The following additional 3D volumes (volumes of
interest, VOI) are frequently used [30,35]. It is
recommended, when possible, to include one of the
following 3D volumes of interests during the data
analysis and reporting:
3D isocontour at 41% of the maximum pixel value
adapted for background (A41)
3D isocontour at 50% of the maximum pixel value (50)
3D isocontour at 50% adapted for background (A50)
3D isocontour at 70% of the maximum pixel value (70)
3D isocontour at 70% adapted for background (A70)
&The isocontour described as A41 generally corresponds
best with the actual dimensions of the tumour, but only
for higher tumour-to-background values and homoge-
nous backgrounds. In practice, however, this VOI
seldom results in useful tumour definition because of
noise, inhomogeneities in tumour and background, and
sometimes low tumour-to-background ratios (low con-
trast between tumour and background). In this case, the
VOI based on a higher isocontour value should be
chosen for all sequential scans of the same patient.
&Other tumour segmentation methods have been de-
scribed for tumour volumetry in literature, such as
gradient-based methods [36], iterative methods [37],
and fuzzy clustering/segmentation methods [38]. These,
however, are not routinely used for determining SUVs
and are not widely available. Yet these new methods
may be used provided that at least the maximum uptake
(SUV
max
) always and, for clinical trials, preferably 2D
SUV
peak
will be determined and reported as well.
&When VOIs are generated semi-automatically, it is often
not possible to generate a reliable VOI if there is a high
Eur J Nucl Med Mol Imaging (2010) 37:181200 193
background or an area of high uptake (bladder, heart)
close to/adjacent to the lesion, or if there is low uptake
in the lesion. Semi-automatically generated VOIs must
therefore be checked visually. If the VOIs are not
reliable and/or do not correspond visually with the
lesion, only the maximum SUV based on a manually
generated VOI and 2D SUV
peak
should be used for
reporting.
Quality control and inter-institution cross-calibration
PET quality control
Both physiological and physical factors influence the
accuracy and reproducibility of standard uptake values
(SUV) in oncology FDG PET studies. Variations in PET
camera calibration, image reconstruction, and data analysis
and/or settings can have more than a 50% effect on the
measured SUV [15]. The use of SUV in multi-centre
oncology PET studies therefore requires an inter-institution
calibration procedure in order to facilitate the exchange-
ability of SUVs between institutions. It is also important
that all participating institutions use methodology that is as
similar as possible. In order to ensure the exchangeability
of SUVs, a minimum set of quality-control procedures must
be carried out, such as:
&Daily quality control
&Calibration/cross-calibration of PET or PET/CT camera
with the institutions own dose calibrator or against
another dose calibrator (e.g. that of an FDG provider)
which is generally used to determine patient specific
FDG activities
&Inter-institution cross-calibration and determining ac-
tivity recovery coefficients
Note that these QC measures do NOT replace any QC
measures required by national law or legislation or those
recommended by local nuclear medicine societies. A brief
summary of PET and PET/CT quality-control procedures,
specifically recommended here to ensure accurate SUV
quantification, is given below.
Daily quality control (Daily QC)
The aim of daily quality control is to determine whether the
PET or PET/CT camera is functioning well; in other words,
to establish detector failure and/or electronic drift. Most
commercial systems are equipped with an automatic or semi-
automatic procedure for performing daily quality controls.
For some PET and PET/CT systems, the daily quality control
includes tuning of hardware and/or settings. Thus both the
procedure and its name may be different between various
PET and PET/CT systems. In all cases, all daily quality-
control measures and/or daily setup/tuning measurements
should be performed according to the manufacturers
specifications. Users should check whether the daily quality
control meets the specifications or passed the test correctly.
When available, a daily PET or PET/CT scan of a
cylindrical phantom filled with a Ge-68 solution may be
collected. Inspection of uniformity and quantitative accura-
cy of the reconstructed image may help to identify technical
failures that were not detected using the routine daily QC
procedures. In addition, sinogram data may be visually
inspected to check detector failures.
Calibration QC and cross-calibration of PET and/or PET/
CT cameras
The aim of calibration and cross-calibration is to determine
the correct and direct calibration of a PET or PET/CT
camera with the institutions own dose calibrator or against
another one which is used to determine patient-specific
FDG activities [39]. If these FDG activities are ordered
directly from and supplied by a pharmaceutical company,
cross-calibration of the PET camera should be carried out
using a calibration sample supplied by that company (i.e.
the customer should order an FDG activity of about
70 MBq, see below, as if it concerns an FDG activity
needed for a clinical study). Remember that cross-
calibration must not be confused with normal calibration.
Cross-calibration is a direct, relative calibration between the
used (or institutions own) calibrator and the PET camera,
and therefore provides information about possible calibra-
tion discrepancies between the PET camera and the dose
calibrator, which is more essential for correct SUV
quantification than the individual calibrations themselves.
Differences of up to 15% in the cross-calibration between
PET camera and dose calibrator have been observed [15]
due to the fact that individual calibrations of the dose
calibrator and the PET camera (usually carried out by the
manufacturer) are performed using different calibration
sources and procedures, and by different companies and/
or persons. This explains the importance of a direct
cross-calibration between the dose calibrator and PET
camera used.
In short, the procedure is as follows: A syringe is filled
with approximately 70± 10 MBq of FDG solution and is re-
measured in a calibrated dose calibrator (or the syringe is
ordered from the pharmaceutical company). The FDG is
then introduced into a calibration phantom with an exact
known volume (<1%) filled with water, which results in a
solution containing an exactly known activity concentration
(Bq/ml). Homogenisation of the FDG in the phantom
should be achieved by leaving an air bubble of approxi-
194 Eur J Nucl Med Mol Imaging (2010) 37:181200
mately 1020 ml within the phantom and subsequently
shaking/mixing the phantom for a short period of time
(10 min). If the institution has a calibrated well counter,
three samples of approximately 0.5 ml should be taken
from the calibration phantom solution using a pipette.
The exact weight/volume of the samples should be
determined before placing the samples in the well
counter. Emission scans of the calibration phantom are
performed with the PET or PET/CT camera using the
recommended whole-body acquisition protocol/procedure
(including multi-bed acquisitions, see Appendix III).
Once the activity has decayed (after an interval of
10 h or more), a transmission scan is performed without
moving the phantom from its position in the PET or PET/
CT system. For PET/CT cameras on which attenuation
correction is performed using a low-dose CT-scan (CT-
AC), the CT-AC scan can be carried out either directly
before or after the emission scan.
Emission scans are reconstructed in accordance with
the recommended reconstruction parameters as described
in Image reconstructionon image reconstruction and
Appendix II. VOI analysis is performed in order to
determine the average volumetric concentration of activity
within the phantom as measured by the PET camera.
Cross-calibration factors between the PET or PET/CT
camera and dose calibrator and well counters can then be
derived directly. Once the cross-calibration procedure has
been completed, conversion factors will be known with
which the counts/measurements for different equipment
can be synchronised. N.B.: The cross-calibration factor
between the PET camera and dose calibrator should be
equal to 1.0 (<10%). A standard operating procedure
(SOP) is described in Appendix III.1 (Software and/or
processing programs for (automated) analysis of the QC
calibration experiments are available on request as
research tool, r.boellaard@vumc.nl).
Image quality and recovery coefficients (IQRC)
Although a correct cross-calibration is guaranteed using
the quality-control procedure described above, differ-
ences in SUV quantification may still occur between
centres as a result of differences in the reconstruction
and data analysis methodology used. In particular,
differences in the final image reconstruction (i.e.
following reconstruction, including all effects due to
filters and pixel size settings, etc.) have, depending on
the shape of the tumour, a significant effect on the SUV
result for smaller (<5 cm diameter) tumours. It is
therefore important to determine the accuracy of the
SUV using a standardized anthropomorphicphantom
containing spheres (tumours) of varying sizes. Phantoms
such as these enable to verify SUV quantification under
clinically relevant conditions. The aim of the IQRC
quality-control procedure is:
&To determine/check the correctness of a calibration and
quantification using a non-standard (calibration) phantom
&To measure activity concentration recovery coeffi-
cientsas a function of sphere (tumour) size.
The IQRC quality-control procedure is carried out
closely in accordance with the image quality, accuracy of
attenuation and scatter correctionsprocedure described in
the NEMA Standards Publication NU 2-2001, Perfor-
mance measurements of positron emission tomographs.
VOIs are defined manually according to this procedure.
However, it is known that automatic definition of 3D
volumes of interest (VOI) based on isocontours using fixed
percentages results in a higher SUV accuracy and precision
than those determined using manually defined ROIs or VOIs
(2,3,6). Therefore, 3D-VOIs are also determined using an
automatic VOI method such as described in Definitions for
volumes of interest (VOI) and regions of interest (ROI):
&3D isocontour at 50% adapted for background correc-
tion (A50)
&Maximum pixel value (max)
The procedure for making this VOI is as follows: Firstly,
the locationof the pixel with the maximum SUVin the tumour
must be determined (manually or semi-automatically). Sec-
ondly, a 3D-VOI is generated automatically based on the
maximum SUV/pixel value and its location with a 3D region
growingalgorithm in which all pixels/voxels above the
defined threshold limit are included. Once a VOI has been
generated for each sphere, the average concentration of
activity (or SUV) for the sphere can also be determined. The
average VOI activity concentration value measured is then
normalized with the actual concentration of activity in the
spheres, which indicates the activity concentration recovery
coefficientper sphere (i.e. the ratio of the measured and
actual concentration of activity as a function of sphere size).
The recovery coefficientis finally defined as a function of
sphere size and VOI definition. A standard operating proce-
dure is presented in Appendix III.2. (Software and/or
processing programs for (automated) analysis of the QC
image quality/recovery experiments are available on request
as research tool, r.boellaard@vumc.nl).
The measured activity concentration recovery coeffi-
cients must meet the specifications given below. These
specifications are based on recovery coefficients measured
according to this protocol on various PET and PET/CT
systems of different vendors [3].
Specifications for activity concentration recovery coef-
ficients (RC) measured according the Image Quality QC
SOP (Appendix III.2). Specifications are given for recovery
Eur J Nucl Med Mol Imaging (2010) 37:181200 195
coefficients obtained using A50 VOI and the maximum
pixel value only.
RC specification for A50
Sphere volume (ml) Expected RC Minimal RC Maximal RC
26.52 0.77 0.71 0.83
11.49 0.73 0.67 0.79
5.57 0.66 0.59 0.73
2.57 0.60 0.53 0.68
1.15 0.45 0.38 0.52
0.52 0.30 0.25 0.35
RC specifications for maximum pixel value
Sphere volume (ml) Expected RC Minimal RC Maximal RC
26.52 0.98 0.88 1.08
11.49 0.95 0.85 1.05
5.57 0.89 0.77 1.01
2.57 0.84 0.75 0.94
1.15 0.63 0.51 0.74
0.52 0.38 0.29 0.46
Minimum frequency of PET quality-control procedures
Procedure Frequency
Daily QC Daily
Cross-
calibration
At least 1× per 3 months and always immediately
following software and hardware revisions/
upgrades and immediately following new setups/
normalisations
IQRC Once per institution participating in a multi-centre trial
and always following software adjustments (especially
adjustments to the reconstruction and/or data analysis
(region of interest) software/hardware) and relevant
PET or PET/CT system hardware changes
CT quality control
&In general, QC for CT scanner (and CT part of PET/CT)
are already defined by the radiological societies and
software and procedures are usually incorporated in the
scanner (software). It is recommended to follow the
QC-CT guidelines as required by national law and/or as
indicated by the (national) radiological societies.
&Several documents and reports on QC-CT have been
published and are listed below for the readersinfor-
mation. An overview of CT-QC is given in e.g. the
Equipment Specificationsand Quality Control
sections of the American College of Radiology Practice
Guideline for the Performance of Computed Tomogra-
phy of the Extracranial Head and Neck in Adults and
Children, the American College of Radiology Practice
Guideline for the Performance of Pediatric and Adult
Thoracic Computed Tomography (CT), and the
American College of Radiology Practice Guideline for
the Performance of Computed Tomography (CT) of the
Abdomen and Computed Tomography (CT) of the
Pelvis and in the IPEM report 91. In addition, CT
performance monitoring guidelines are also given in the
American College of Radiology Technical Standard for
Medical Physics Performance Monitoring of Computed
Tomography (CT) Equipment.
Additionally recommended quality-control measures,
specifically for PET or PET/CT systems
&Alignment of PET and CT images on a PET/CT system
should be checked following manufacturers procedure
and frequency.
&Setup and normalisation for both PET and CT should be
performed according to procedure and frequency as
recommended by the manufacturer.
&All devices involved (PET and PET/CT cameras, dose
calibrators, well counters, clocks, scales) should be
maintained according to the manufacturers recommen-
dations. This includes preventive and corrective main-
tenance required to ensure correct and accurate
functioning of the devices.
&Calibration of the above-mentioned devices should
always be performed or correct (cross)calibration
should be verified (by means of QC) after maintenance
and software upgrades.
&Dose calibrators and well counters should be calibrated
at least once per year.
&The accuracy of scales used to weigh patients should be
checked.
Acknowledgements The review contributions of the EANM Do-
simetry Committee and the EANM Radiopharmacy committee are
highly appreciated. Moreover, the authors would like to thank the
European Society of Radiology (ESR) experts for reviewing the CT
dosimetry section. In addition, the reviews by the EANM National
Society delegates are highly appreciated.
Open Access This article is distributed under the terms of the
Creative Commons Attribution Noncommercial License which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided the original author(s) and source are credited.
Appendix I: Examples of FDG activity calculations
Calculation of FDG activity to be administered, example 1:
&3D system with a bed overlap of less than 25% (e.g.
Siemens and GE cameras).
&Patient weighing 70 kg
196 Eur J Nucl Med Mol Imaging (2010) 37:181200
&Scanning duration per bed position: 3 min per bed.
The FDG activity to be administered is therefore:
13.8 (MBq/kg per min/bed) × 70 (kg)/3 min=bedðÞ¼
13:870=3¼322 MBq.
Calculation of FDG activity to be administered, example 2:
&3D PET or PET/CT system with 50% bed overlap (e.g.
Philips cameras).
&Patient weighing 70 kg
&Scanning duration per bed position: 3 min per bed.
The FDG activity to be administered is therefore: 6.9
(MBq/kg per min/bed)×70 (kg)/3 min=bedðÞ¼
6:970=3¼161 MBq.
Note: the scanner brands are solely given as examples. The
key factors in determining the FDG activity are the mode of
acquisition (2D or 3D), the time per bed position (time/bed)
and the degree ofbed overlap and, finally, the patients weight.
In order to simplify implementation in a routine clinical
setting, a Table in 10-kg steps may be used such as published
by Boellaard et al. [3]. Note however that in the present
guideline, a maximum FDG activity of 529 MBq for patients
above 90 kg is recommended. Moreover, a maximum
allowed FDG activity may be applicable by national law.
In the latter case, i.e. for obese patients, increase of scanning
time should be applied to obtain sufficient image quality and/
or to remain within (national) legal limits.
Appendix II: Indicative reconstruction settings
for current PET and PET/CT systems (as of mid 2009)
Here a number of indicative settings are given for different
system types. These indicative settings usually provide
results that meet closely the QC specifications as defined
later in this guideline. In case these reconstructions cannot
be set exactly as indicated below, settings may be set as
close as possible to the ones listed below. However, note
that reconstructions should be set such that they meet the
multi-centre QC specifications for both calibration and
image quality/SUV recovery as function of sphere size (see
Exceptions/special features)
Siemens/CTI systems:
&2D or 3D OSEM reconstruction with sufficient conver-
gence (generally, product of iterations and subset larger
than 50 is sufficient)
&5-mm FWHM Gaussian reconstruction filter in all
directions or equivalent filters. In case of resolution
modeling during reconstruction, a smoothing filter
mayberequiredtomeetthemulti-centreQCspeci-
fications. This filter may be applied afterwards (and/
or thus create an additional dataset).
&matrix size of 128×128 up to 256× 256
&zoom=1
General Electric systems:
&2D or 3D OSEM reconstruction with sufficient conver-
gence (generally, product of iterations and subset larger
than 50 is sufficient)
&5-mm FWHM Gaussian filter in all directions or
equivalent filters. In case of resolution modeling during
reconstruction, a larger filter may be required to meet
QC specifications. This filter may be applied afterwards
(and/or thus create an additional dataset)
&matrix size 128×128 up to 256× 256
&zoom=1
Philips systems (Gemini, Gemini ToF):
&There are two options:
(1) Gemini TF: LOR-TF-RAMLA (Blob-OS-TF) with
normalsmoothing setting.
(2) Gemini (non ToF): LOR-RAMLA using default
settings (as of mid-2006).
(3) For both use an image matrix size of 144×144
Appendix III: Standard operating procedures
for quality control
Calibration QC of PET and PET/CT and information
required for calibration report form
Materials
&About 30 to 70 MBq
18
F-FDG
&Cylindrical calibration phantom, any dimension but
with exactly known volume
&PET or PET/CT system. Phantom volume of about
69 l, diameter from 1525 cm.
&Dose calibrator (DC)
Site/other information
Site ID =
System type and model =
System software version =
Volume of calibration phantom = (ml)
Scan date = (dd:mm:yyyy)
Scan time = (hh:mm:ss)
Time difference between DC and PET = (min:ss)
OR
Time difference between official time* and PET = (min:ss)
Time difference between official time* and DC = (min:ss)
*Official time = atomic clock (may be taken from internet
in case of FDG)
Eur J Nucl Med Mol Imaging (2010) 37:181200 197
Preparation
&Preparea5to10mlsyringewithabout70MBqFDG,
provide the exact measured amount of FDG activity
below
&FDG activity = ............................(MBq) specified at
.......................(hh:mm:ss)
&Fill calibration phantom completely (with water) and
then remove 10 ml water from the phantom
&Put the FDG in the phantom. Make sure that all
activity is in the phantom by flushing the syringe a
few times.
&Extensively shake the phantom to homogenize activity
throughout the phantom
PET or PET CT scan acquisition
&Put phantom in the PET or PET/CT system
&Acquire a PET or PET/CT scan consisting of at least
two PET bed positions. PET and PET/CT scan
acquisition and reconstruction should be performed
identically to patient studies as prescribed in the
clinical protocol. However, somewhat longer acquis-
itions are recommended (e.g. 5 to 10 min per bed
position acquisitions), include a standard transmis-
sion or (low-dose) CT for attenuation correction
purposes.
Reconstructions
Reconstructions should be performed with attenuation,
scatter, normalisation, decay, dead time corrections, i.e. all
corrections required for quantification. Follow the instruc-
tions given in this guideline (Image reconstruction).
Analysis
Determine average activity concentration or SUV within
the phantom. Verify that activity concentration and/or SUV
are within 10% of expected values.
Pitfalls
&Make sure that all clocks (of dose calibrator and PET or
PET/CT system) are synchronized. Consult your local
service engineer when needed. Clocks should be
synchronized with the official local time within 1 min
(in case of FDG studies).
&Remaining activity in the syringe will result in incorrect
verification of PET or PET/CT system calibration.
&If count rates exceed the limits of the PET or PET/CT
system to allow for accurate quantification due to high
dead time or randoms fractions, then this experiment
should be performed using a lower FDG activity and/or
prepare the phantom a couple of hours in advance to
allow for radioactive decay.
CRF/SOP image quality and activity concentration
recovery coefficient PET
Date = ..........................(dd:mm:yyyy)
Site ID = ...........................
Time difference between DC and PET = (min:ss)
OR
Time difference between official time and PET = (min:ss)
Time difference between official time and DC = (min:ss)
Materials
&Various
18
F-FDG activities in 25 ml syringes, two
syringes with 20 MBq specified at expected phantom
acquisition time.
&Bottle filled with exactly 1,000 ml
&NEMA NU2-2001 (Patient preparationof this NEMA
standard) Image Quality phantom
&Dose calibrator (=DC)
Preparation
Stock/solution for spheres:
&Fill bottle with exactly 1,000 ml water
&Add 20 MBq
18
F-FDG. Make sure all activity is
removed from the syringe into the phantom.
FDG activity = .........................................MBq speci-
fied at ................... (hh:mm:ss)
Volume (of FDG in syringe) = ...................................... (ml)
&Homogenize solution (20 MBq FDG in 1,000 ml)
&Fill all spheres of the NEMA NU2-2002 image quality
phantom with this solution.
Filling of background compartment of image quality
phantom:
&Fill background compartment completely with water
&Remove 30 ml water from the background compartment
of the phantom
&Add 20 MBq FDG in the background compartment.
Make sure all activity is removed from the syringe into
the phantom.
&FDG activity = .........................................MBq speci-
fied at ................... (hh:mm:ss)
&Homogenize the solution in the background compart-
ment by shaking the phantom extensively.
198 Eur J Nucl Med Mol Imaging (2010) 37:181200
PET or PET/CT Scans
&Acquire a routine quantitative whole-body FDG PET scan of
at least two PET bed positions of the entire phantom. Follow
instructions given in this guideline for the patient studies (i.e.
standard acquisition parameters and scan durations).
&Acquire a quantitative whole-body FDG PET scan of
one PET bed position of the phantom. Position the
phantom such that spheres are located at the centre of
the axial field of view. In this case, emission scans per
bed position should take at least 10 min. All other scan
parameters must be identical to those used during
patient scanning and as recommended in this guideline.
&PET scan acquisition time = ......................... (hh:mm:ss)
&PET scan acquisition date = .................... (dd:mm:yyyy)
Reconstructions
Reconstructions should be performed with attenuation,
scatter, normalisation, decay, dead time corrections, i.e. all
correction needed for quantification. Reconstructions need to be
performed conform specifications given in this guideline. In
case such a protocol is not in place, the recommendation for
quantitative studies as provided by the vendor should be applied.
Analysis
Determine recovery coefficient as function of sphere
using maximum pixel value and A50 VOI.
Other recommendations
If the department has a calibrated well counter available
(see calibration procedure), this is the tool of preference with
which to determine/verify the exact concentration of activity
in the spheres and in the background of the phantom.
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