Head-to-Head Comparison of Tc-99m-sestamibi SPECT/CT and C-11-L-Methionin PET/CT in Parathyroid Scanning Before Operation for Primary Hyperparathyroidism

Abstract

Purpose:
The preferred nuclear medicine method for identification of hyperfunctioning parathyroid glands in hyperparathyroidism (HPT) develops continuously in relation to the technological progress. Diagnostic methods based on PET/CT have during recent years evolved with new tracer possibilities competing with traditional scintigraphic methods. This investigation is a head-to-head comparison of Tc-99m-sestamibi SPECT/CT gamma camera scintigraphy (sestamibi SPECT/CT) and C-11-L-methionin PET/CT imaging (methionine PET/CT) for preoperative identification of hyperfunctioning parathyroid glands.

Procedures:
The study is a prospective cohort study including 27 patients diagnosed with primary hyperparathyroidism (PHPT). Two nuclear medicine physicians assessed all examinations independently and blinded. All scanning assessments were matched to the final surgical diagnosis as confirmed by histopathology. Biochemical monitoring of the therapeutical effects was performed preoperatively by PTH-measurements and followed postoperatively for up to 12 months. Comparisons were made for differences in sensitivity and positive predictive value (PPV).

Results:
Twenty-seven patients (18 females, 9 males; mean age (range): 58.9 years (34.1-79)) were enrolled into the study. The 27 patients had a total of 33 identified sites of lesions of which 28 (85%) turned out to be histopathological verified hyperfunctioning parathyroid glands. The sensitivity and PPV for sestamibi SPECT/CT were 0.71 and 0.95; that of methionine PET/CT was 0.82 and 1, respectively. Both sensitivity and PPV were slightly lower for sestamibi SPECT/CT than for methionine PET PET/CT (-0.11, 95% confidence interval (95% CI): -0.29 to 0.08; -0.05, 95% CI: -0.14 to 0.04, respectively), but not to a statistically significant extent (p=0.38 and p=0.31). The sensitivity and PPV for diagnostic CT were 0.64 (95% CI: 0.44 to 0.81) and 1 (95% CI: 0.81 to 1).

Conclusions:
Methionine PET/CT performed comparable to sestamibi SPECT/CT with respect to identification and localization of hyperfunctioning parathyroid glands prior to surgery.

Full text

Vol.:(0123456789)
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Molecular Imaging and Biology
https://doi.org/10.1007/s11307-023-01808-7
RESEARCH ARTICLE
Head‑to‑Head Comparison ofTc‑99m‑sestamibi SPECT/CT
andC‑11‑L‑Methionin PET/CT inParathyroid Scanning Before
Operation forPrimary Hyperparathyroidism
SysVestergaard1,2 · OkeGerke1,3· MetteBay4· AndersRørbækMadsen4· LisStilgren5· CharlotteEjersted6·
KateIsabellaRewers1· NickJakobsen1· JonThorAsmussen7· Poul‑ErikBraad8· HenrikPetersen9·
AndersThomassen1,9· SørenSchifter1
Received: 16 November 2022 / Revised: 15 February 2023 / Accepted: 23 February 2023
© The Author(s), under exclusive licence to World Molecular Imaging Society 2023
Abstract
Purpose The preferred nuclear medicine method for identification of hyperfunctioning parathyroid glands in hyperparathy-
roidism (HPT) develops continuously in relation to the technological progress. Diagnostic methods based on PET/CT have
during recent years evolved with new tracer possibilities competing with traditional scintigraphic methods. This investigation
is a head-to-head comparison of Tc-99m-sestamibi SPECT/CT gamma camera scintigraphy (sestamibi SPECT/CT) and C-11-
L-methionin PET/CT imaging (methionine PET/CT) for preoperative identification of hyperfunctioning parathyroid glands.
Procedures The study is a prospective cohort study including 27 patients diagnosed with primary hyperparathyroidism
(PHPT). Two nuclear medicine physicians assessed all examinations independently and blinded. All scanning assessments
were matched to the final surgical diagnosis as confirmed by histopathology. Biochemical monitoring of the therapeutical
effects was performed preoperatively by PTH-measurements and followed postoperatively for up to 12 months. Comparisons
were made for differences in sensitivity and positive predictive value (PPV).
Results Twenty-seven patients (18 females, 9 males; mean age (range): 58.9 years (34.1–79)) were enrolled into the study.
The 27 patients had a total of 33 identified sites of lesions of which 28 (85%) turned out to be histopathological verified
hyperfunctioning parathyroid glands. The sensitivity and PPV for sestamibi SPECT/CT were 0.71 and 0.95; that of methio-
nine PET/CT was 0.82 and 1, respectively. Both sensitivity and PPV were slightly lower for sestamibi SPECT/CT than for
methionine PET PET/CT (−0.11, 95% confidence interval (95% CI): −0.29 to 0.08; −0.05, 95% CI: −0.14 to 0.04, respec-
tively), but not to a statistically significant extent (p=0.38 and p=0.31). The sensitivity and PPV for diagnostic CT were 0.64
(95% CI: 0.44 to 0.81) and 1 (95% CI: 0.81 to 1).
Conclusions Methionine PET/CT performed comparable to sestamibi SPECT/CT with respect to identification and localiza-
tion of hyperfunctioning parathyroid glands prior to surgery.
Keywords Sestamibi SPECT/CT· C-11-L-methionine PET/CT· Hyperparathyroidism· Primary hyperparathyroidism·
Hyperfunctioning parathyroid glands
* Sys Vestergaard
Sys.Vestergaard@rsyd.dk
1 Department ofNuclear Medicine, Odense University
Hospital, Odense, Denmark
2 Open Patient data Explorative Network, Department
ofClinical Research, University ofSouthern Denmark,
Odense, Denmark
3 Research Unit ofClinical Physiology andNuclear Medicine,
Department ofClinical Research, University ofSouthern
Denmark, Odense, Denmark
4 Department ofORL - Head & Neck Surgery andAudiology,
Odense University Hospital, Odense, Denmark
5 Department ofMedicine, Endocrinology, Odense University
Hospital, Svendborg, Denmark
6 Department ofEndocrinology, Odense University Hospital,
Odense, Denmark
7 Department ofRadiology, Odense University Hospital,
Odense, Denmark
8 Diagnostic Imaging, Medico, Aabenraa, Denmark
9 Røntgen og Skanning, Hospital ofSouthern Jutland,
Aabenraa, Denmark

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Introduction
Preoperative localization of hyperfunctioning parathyroid
tissue is still a diagnostic problem with room for improve-
ment. Different imaging modalities are used, primarily
ultrasound and nuclear medicine imaging [1–4]. In nuclear
medicine PET-scanning has been proposed as a technology
with potential for improvement of the traditional gamma
camera-based imaging investigations but the potential of
PET scanning compared to gamma camera investigations
needs further clarification [5–7].
We have performed a head-to-head comparison of Tc-
99m-sestamibi SPECT/CT gamma camera scintigraphy
(sestamibi SPECT/CT) and C-11-L-methionin PET/CT
(methionine PET/CT) for preoperative localization of hyper-
functioning parathyroid tissue in patients diagnosed with
primary hyperparathyroidism (PHPT).
These two techniques are the preferred imaging modali-
ties for localization of hyperparathyroidism lesions; cur-
rently, there are no clear evidence for one of them being
superior to the other.
Materials andMethods
The study is a prospective, blinded, head-to-head compari-
son of sestamibi SPECT/CT parathyroid scans compared
to methionine PET/CT. The two nuclear medicine imaging
modalities were additionally compared to the diagnostic CT
scan performed as part of the PET/CT. Both imaging proce-
dures were performed within 14 days to secure comparable
diagnostic conditions.
Patient Flow
Adult patients with PHPT referred for preoperative localiza-
tion of potential hyperfunctioning parathyroid tissue from
two endocrinology departments located at two different
departments (both part of Odense University Hospital in
the Region of Southern Denmark) between April 2016 and
December 2018 were candidates for inclusion. The diagno-
sis PHPT is based on repetitive measurements of elevated
serum calcium-ion and elevated PTH or PTH in the upper
1/3 of the normal range combined with no relevant differ-
ential diagnosis. The hospital receives unselected patients
from the Region of Southern Denmark. Patients were invited
to participate in the study after confirmation of inclusion
criteria i.e., the diagnosis of PHPT and indication for par-
athyroidectomy. Exclusion criteria were age < 18 years,
inability to cooperate, e.g., due to claustrophobia, preg-
nancy or breast feeding, inability to give informed consent
and/or due to known allergy to iodine-containing contrast.
Sestamibi SPECT/CT parathyroid scan was performed prior
to methionine PET/CT due to iodine-containing contrast
agent used during the latter. Both modalities were assessed
in the routine settings independently and mutually blinded
by two nuclear medicine physicians and never by the same
nuclear medicine physician/trainee for the two modalities
and the same patient. A specialist in radiology evaluated
the diagnostic CT scan independently and blinded to the
nuclear medicine assessments. All evaluations were per-
formed blinded to the available related investigations includ-
ing ultrasound (US). The assessment was documented on
a phantom drawing of the thyroid gland divided in fields
indicating “cranial/caudal dexter,” “cranial/caudal sinis-
ter,” “aberrant foci,” and “no adenomas detected,” as well
as evaluation 1–5 for each adenoma assessment (1: very
likely negative; 2: likely negative; 3: ambiguous; 4: likely
positive; 5: very likely positive). After imaging, the patient
flow followed the usual routine, with the only difference that
there was a similar assessment performed by the surgeon
post-surgery, and that the endocrinologist evaluated follow
up blood samples and histopathology to confirm or reject the
pre- and peroperative findings.
Tracers, Image Acquisition, andScanners
The local standard preoperative localization procedure, ses-
tamibi SPECT/CT, is compared to C-11-methionine PET/
CT and diagnostic CT. All imaging methods are performed
routinely at the department, but C-11-methionine PET/CT
and diagnostic CT has not previously been used locally for
localization of hyperfunctioning parathyroid tissue. A typi-
cal example of the three imaging modalities compared is
shown in Fig.1.
Tc‑99m‑Sestamibi SPECT/CT Parathyroid Scanning
The standard parathyroid scintigraphy at our department
consists of a dual tracer 99mTcO4/99mTc-sestamibi and
a dual phase SPECT/low dose CT. The procedure consists
of intravenous injection of 150 MBq Tc-99m-pertechnetat
15 min before doing 5-min statical anterior and posterior
acquisition without zoom, over the thyroid gland, salivary
glands, and including as much of thorax as possible. With
the patient in unchanged position in the scanner, 700 MBq
Tc-99m-sestamibi/Medi-mibi from Wiik Pharma (Stamicis)
and 200 mg sodium perchlorate is injected iv 15 min before
doing planar scintigraphy in 8 min (early MIBI-acquisition),
followed by SPECT/CT of the collum and thorax (15 + 3
min) and finally another 8-min statical acquisition (late
MIBI-acquisition).
We used two different SPECT/CT-scanners, both double-
headed gamma cameras equipped with low-energy, parallel

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hole high-resolution collimators (LEHR). One is a GE Dis-
covery 670 SPECT/CT scanner and the other a Siemens
Symbia T16 scanner. On both scanners we obtained ante-
rior and posterior planar images (matrix 256 × 256), 8 min/
image) of the neck and thorax and SPECT/CT (matrix 256
× 256, 64 projections, 20 s/projection) as mentioned before.
C‑11‑L‑Methionin PET/CT Parathyroid Scanning
PET/CT data was acquired on a GE Discovery 690 or 710
PET/CT scanner. Imaging was performed 20 minutes post-
injection using C-11-Methionin (6–8 MBq/kg bodyweight)
over 2–3 bed positions, a slice overlap of 11 and an acqui-
sition time of 10 minutes per bed position. The scan field
of view was 70 cm. Attenuation correction was based on
a low-dose CT scan. The PET data was reconstructed into
transaxial slices with a matrix size of 256×256 (pixel size
2.74 mm) and a slice thickness of 3.27 mm using iterative
3D OS-EM (3 iteration, 24 subsets) with corrections for
time-of-flight (GE VPFX) and point-spread-blurring (GE
sharpIR). Corrections for attenuation, randoms, deadtime,
and normalization were done inside the iterative loop. Fol-
lowing the hybrid PET/CT scan a helical diagnostic CT scan
was acquired over the same region with in-vivo contrast
(Ultravist 370 mg I/ml) using a standard CT protocol with a
scan field of view of 50 cm.
Surgery
Surgery was performed within 12 months after investigation.
All procedures were performed by head and neck specialists
with extensive experience in parathyroid gland surgery. Only
the Sestamibi SPECT/CT result was available for the sur-
geon at the time of the procedure, but an US was performed
preoperatively.
Successful surgery was confirmed by a decline in the
peroperative PTH concentration of ≥ 50% from the highest
preoperative level according to the Miami-criteria [8] and/or
per- or post-operative histopathology indicating hyperfunc-
tion of the parathyroid tissue, either adenoma or hyperplasia.
The number and locations of the removed parathyroid glands
were registered by the surgeon.
The surgeon postoperatively performed assessment of the
localization of the hyperfunctioning parathyroid tissue com-
pared to the routine imaging procedures used and including
Likert scale rating [9]. Positive findings were combined with
the PTH measurements performed peroperatively and the
concluding histopathology.
Fig. 1 Illustration of parathyroid adenoma localization with the three investigated imaging modalities. SPECT: Tc-99m-sestamibi SPECT/CT,
PET/CT: C-11-L-methionin PET/CT, CT: Contrast CT

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Reference Standard
The reference standard for evaluation of the imaging modali-
ties was defined as the combined conclusion of the peropera-
tive findings that is the surgeon’s assessment and localization
of peroperatively removed tissue including the final histo-
pathological diagnosis.
Follow‑up
The patients were followed with relevant blood tests for
12 months postoperatively. Standard follow up of ionized
calcium and PTH measurements were part of the evalua-
tion, conventionally performed 3 weeks, 3, 6, and 12 months
postoperatively. The laboratory tests were used to monitor
successful surgical outcome defined as persistent normaliza-
tion of ionized calcium and PTH measurements for at least
6 months.
Ethics
The study was performed in accordance with Good Clini-
cal Practice (GCP) and the Helsinki Declaration. The Dan-
ish Medicines Agency approved the study protocol and its
addendum (journal no. 2014052699 and 2015110386). The
Scientific Ethics Committee of the Region of Southern Den-
mark approved the conduct of the study and its informed
consent form (project ID: S-20130046), and The Danish
Data Protection Agency approved the data collection.
Statistics
Descriptive statistics were applied according to data type;
continuous variables were presented as mean ± standard
deviation (SD), categorical variables by frequencies and
respective percentages.
Identification of adenomas and/or hyperplasia vs. normal
histology was analyzed on a per-lesion basis by sensitivity,
specificity, positive predictive value (PPV), negative predic-
tive value (NPV), and accuracy (sum of true positive and
true negative findings divided by all observations). Point
estimates were supplemented by conservative Clopper-Pear-
son-type 95% confidence intervals (95% CIs). Exploratory
testing of between-modality comparisons was done with
McNemar’s test for differences in sensitivity, specificity,
and accuracy, whereas an approximate test was employed
for differences in PPV and NPV [10, 11].
The study was originally planned to include 60 patients to
achieve sufficient precision in the estimation of the sensitiv-
ity and the positive predictive value for the modalities under
consideration, including an interim analysis with 30 patients.
The recruitment of patients was terminated following the
interim analysis showing that significant differences would
not be obtained by including the planned number of patients.
The level of significance is 5%. All analyses were per-
formed with STATA/MP 17.0 (StataCorp, College Station,
Texas 77845 USA).
Results
Twenty-seven patients (18 females, 9 males; mean ± SD
age: 58.9 ± 11.5 years; age range: 34.1 to 79 years) met
the criteria for inclusion and were enrolled into the study
(Table1). None had prior surgery or radiation performed to
the neck, and none were diagnosed with multiple endocrine
neoplasia syndrome or familiar hyperparathyroidism. Ten
patients were treated with vitamin-D and calcium supple-
ments, which may indicate kidney affection, but without
fulfilling the exclusion criteria, two patients were treated
with thiazide and none with cinacalcet.
The 27 patients had 33 foci removed as shown in Suppl.
Table1 and 2 (ESM). Of these 28 (85%) were verified by
histopathology to be hyperfunctioning parathyroid tissue.
Twenty-one patients had a single focus removed, 17 adeno-
mas and four hyperplasia. Two separate foci were extirpated
in each of six patients.
The sensitivity (95% CI) and PPV (95% CI) for sesta-
mibi SPECT/CT was 0.71 (0.51–0.87) and 0.95 (0.76–1);
and for methionine PET/CT 0.82 (0.63–0.94) and 1
(0.85–1), respectively (Table2). Both sensitivity (−0.11
(−0.29–0.08)) and PPV (−0.05 (−0.14–0.04)) were less
for sestamibi SPECT/CT than for methionine PET/CT,
but not statistically significant (p=0.38 and p=0.31).
Table 1 Demographics and baseline characteristics of study popula-
tion (N=27)
Variable Descriptive statistics
Gender 18 females (67%), 9 males (33%)
Age, years 58.9 ± 11.5
Center Department 1: 18 (67%) /
Department 2: 9 (33%)
Known comorbidity 10 (37%)
D-vitamin deficiency 6 (22%)
Multinodular dysthyreosis 0 (0%)
Known kidney disease 2 (7%)
Medication before operation 10 (37%)
Mimpara 0 (0%)
D-vitamin 9 (33%)
Calcium 5 (19%)
Lithium 0 (0%)
Thiazide 2 (7%)

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The sensitivity and PPV for diagnostic CT were 0.64
(0.44–0.81) and 1.00 (0.81–1.00). Diagnostic CT accord-
ingly performed slightly worse than sestamibi SPECT/CT
in terms of sensitivity (0.07 (−0.13–0.28; p=0.69), but
slightly favorable in terms of PPV (−0.05 (−0.14–0.04);
p=0.31), both comparisons are non-significant.
Independent and mutual blinded assessment performed
by two nuclear medicine physicians for each of the two
nuclear medicine imaging modalities showed a high
degree of compliance. For sestamibi SPECT/CT the agree-
ment between the two independent assessors was 93% and
for methionine PET/CT 85%.
Of the 17 single parathyroid adenomas sestamibi
SPECT/CT identified 16 (94%) and of the four single
hyperplastic foci sestamibi SPECT/CT identified two.
Peroperatively, 6 patients were suspected having more
than one focus. In 2 of the 6 patients, histopathology veri-
fied hyperplasia in two foci for each patient, while sesta-
mibi SPECT/CT and/or methionine PET/CT only identi-
fied one of the two foci in each. In three of the remaining
four patients, who peroperatively were suspected having
two adenomas, histopathology verified only one adenoma
in two patients according to the location identified by
the two nuclear medicine imaging modalities. The third
patient in agreement with imaging also had only one his-
topathologically suspected focus which was classified as
‘probably normal tissue. However, a peroperative post-
extirpation PTH decline of 85% supported that the imag-
ing diagnosis was correct (ID 105; as shown in the Suppl.
Table2 (see ESM)). The last patient suspected of double
adenoma had histopathology that did not confirm adeno-
mas or hyperplasia in any of the suspected locations. This
also corresponded to the negative findings with both imag-
ing modalities (ID 109; as shown in the Suppl. Table2
(see ESM)).
Methionine PET/CT identified 16(94%) of the 17 single
adenomas and three of the four hyperplastic foci identified
during surgery.
One of the hyperplastic foci, which was not localized by
either of the imaging modalities, weighed only 92 mg, which
is in the reported lower end of the diagnostic weight range
for foci diagnosed by sestamibi SPECT/CT imaging [12].
However, despite the size an adenoma of 302 mg was also
not identified by either of the imaging modalities. But in
this case, the elevated serum PTH concentration, 7.8 pmol/L
(normal range 1.6-6.9 pmol/L), supported the histological
diagnosis. In contrast, an adenoma of 82 mg was local-
ized by methionine PET/CT, but not by sestamibi SPECT/
CT, while an adenoma of 3.054 mg was not localized by
methionine PET/CT, but by sestamibi SPECT/CT. In this
last case, the preoperative PTH plasma concentration was
17.1 pmol/L.
Follow-up measurements of plasma ionized calcium
and serum PTH 3, 6, and 12 months after surgery showed
normalization in 26 of 27 patients (96%). One patient with
normal histological diagnosis did not return to normal levels
of ionized calcium. This patient had a preoperative ionized
calcium of 1.47 mmol/L (normal range: 1.18–1.32 mmol/L)
and PTH of 8.9 pmol/L (normal range: 1.6-6.9 pmol/L).
Postoperatively the PTH level was normalized, 5.2 pmol/L,
but ionized calcium remained elevated at 1.44 mmol/L.
Discussion
Methionine PET/CT performed comparable to sestamibi
SPECT/CT with respect to identification and localization
of hyperfunctioning parathyroid glands prior to surgery.
Methionine PET/CT performed slightly better than ses-
tamibi SPECT/CT with respect to sensitivity and PPV, but
Table 2 Diagnostic accuracy of adenoma detection (N=33 adenomas in 27 patients)
CI confidence interval, FN false negative, FP false positive, TN true negative, TP true positive
Parameter Sestamibi SPECT/
CT, nuclear medicine
specialist (rater 1)
Methionine PET/
CT, nuclear medicine
specialist (rater 2)
Diagnostic CT,
radiology specialist
(rater 3)
Difference between
rater 1 and 2
Difference between
rater 1 and 3
Sensitivity (95% CI);
TP/(TP + FN)
0.71 (0.51–0.87) 0.82 (0.63–0.94) 0.64 (0.44–0.81) −0.11 (−0.29–0.08);
p=0.38
0.07 (−0.13– 0.28;
p=0.69
Specificity (95% CI);
TN/(TN + FP)
0.8 (0.28–0.99) 1 (0.48–1) 1 (0.48–1) −0.2 (−0.75–0.35);
p=0.99
−0.2 (−0.75–0.35);
p=0.99
PPV (95% CI); TP/
(TP + FP)
0.95 (0.76–1) 1 (0.85–1) 1 (0.81–1) −0.05 (−0.14–0.04);
p=0.31
−0.05 (−0.14–0.04);
p=0.31
NPV (95% CI); TN/
(TN + FN)
0.33 (0.10–0.65) 0.5 (0.19–0.81) 0.33 (0.12–0.62) −0.17 (−0.36–0.03);
p=0.10
0 (−0.15–0.15); p=0.99
Accuracy (95%
CI); (TP +TN)/
(TP+FN+TN+FP)
0.73 (0.54–0.87) 0.85 (0.68–0.95) 0.70 (0.51–0.84) −0.12 (−0.29–0.05);
p=0.22
0.03 (−0.16–0.22);
p=0.99

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the differences are not statistically significant. Independent
and mutual blinded evaluations by two nuclear medicine
physicians of the scintigraphic and PET imaging modali-
ties were highly concordant. The Independent radiological
evaluation of the diagnostic CT scan performed compara-
bly to the methionine PET/CT and sestamibi SPECT/CT.
Both nuclear medicine modalities failed in identifying
more than one hyperfunctioning focus in patients with
more than one focus removed during surgery. Possible
explanations are size of the hyperplastic foci and possi-
ble non-metabolic phase of the hyperplasic cells [13, 14].
Moreover, the assessing imaging specialist may be biased
to conclude the search early after finding one suspected
hyperfunctioning lesion.
The preferred imaging methods for presurgical localiza-
tion of PHPT lesions are developing continuously. Sesta-
mibi SPECT/CT and methionine PET/CT have until now
been the preferred routine techniques without clear prefer-
ence for either of these [15, 16]. However, investigations
have demonstrated added value of methionine PET/CT for
localization of parathyroid adenomas in case of equivocal
or negative sestamibi SPECT/CT [6, 17, 18].
The high agreement between mutual blinded double
assessments of the nuclear medicine imaging modalities
shows robustness of the procedures, thereby supporting
independence of the assessor’s experience. This is an
important preferable characteristic for analyses used in
daily clinical practice.
More recent investigations have shown superior accu-
racy for F-18 fluorocholine PET/CT (choline PET/CT)
compared to sestamibi SPECT/CT [19, 20], and an inves-
tigation including patients with negative or inconclusive
sestamibi SPECT/CT suggests that choline PET/CT has a
better performance than methionine PET/CT for the detec-
tion of pathological parathyroid tissue [21]. This finding
is supported by a recent meta-analysis, but without direct
comparison in any of the included papers [22]. Another
recent meta-analysis concluded that Choline PET/CT was
the best performing technique of all compared [23].
Sestamibi SPECT/CT is the departments default
approved tracer for this indication and at present the
department has no regulatory approval for Choline PET/
CT. However, a direct blinded head-to-head comparison of
methionine PET/CT to Choline PET/CT without preselec-
tion of patients is still lacking. Therefore, it is impossible,
based on the current knowledge, to choose a preferred of
the two.
Alternatively, 4D-Ultrasound is another advancing tech-
nique with hands-on advantages [1]. The promising results
of this technique combined with the surgeon’s direct involve-
ment in this investigation is likely to make this method com-
bined with methionine PET/CT or choline PET/CT the cur-
rently recommended presurgical imaging package for pHPT.
Both SPECT/CT and PET/CT combine the anatomical
and functional findings related to hyperfunctioning parathy-
roid tissue, which in addition is supported by the anatomical
information from the CT scan. The quality of the accompa-
nying CT scan is therefore likely to influence the assessment.
In the current investigation only the PET-related CT scan
was performed with contrast. However, the imaging modali-
ties show high diagnostic precision for the combined inves-
tigation irrespective of the quality difference of the CT scan
for the sestamibi SPECT/CT and the methionine PET/CT.
Among diagnostic relevant investigations with non-signif-
icant differences in diagnostic precision the less costly, less
laborious, and less time-consuming is the obvious choice
for routine use. Therefore, at this department Methionine
PET/CT now is the currently preferred nuclear medicine
method for presurgical identification of PHPT adenomas, as
the marginal costs per investigation are minimal when PET/
CT scanners, prioritized capacity, radiochemical production
capacity and expertise are available.
In conclusion, methionine PET/CT performed compara-
ble to sestamibi SPECT/CT with respect to identification
and localization of parathyroid adenomas prior to surgery.
The locally preferred diagnostic method depends on the
equipment and facilities available. Further studies are war-
ranted for evaluation of a potential superiority of one spe-
cific PET tracer.
Supplementary Information The online version contains supplemen-
tary material available at https:// doi. org/ 10. 1007/ s11307- 023- 01808-7.
Acknowledgements The authors would like to thank the involved per-
sonnel of the Department of Nuclear Medicine, Odense University
Hospital for their dedicated support of this study.
Author Contribution S.V. and S.S.: conception of the work. O.G.: sta-
tistical analysis. M.B., A.R.M., L.S., C.E., K.I.R., N.J., J.T.A., P.E.B.,
H.P., A.T.: acquisition, analysis, and interpretation of data. S.V.: manu-
script draft. All authors revised the manuscript critically for important
intellectual content, approved the version to be published, and agreed
to be accountable for all aspects of the work in ensuring that questions
related to the accuracy or integrity of any part of the work are appro-
priately investigated and resolved.
Declarations
Conflict of Interest The authors declare no competing interests.
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