Chemotherapy-induced Cardiac 18 F-FDG Uptake in Patients with Lymphoma: An Early Metabolic Index of Cardiotoxicity?

Abstract

Background: It is uncertain whether myocardial fluorodeoxyglucose uptake occurs solely due to physiological features
or if it represents a metabolic disarrangement under chemotherapy.
Objective: To investigate the chemotherapy effects on the heart of patients with lymphoma by positron emission
tomography associated with computed tomography scans (PET/CT) with 2-deoxy-2[18F] fluoro-D-glucose (18F-FDG
PET/CT) before, during and/or after chemotherapy.
Methods: Seventy patients with lymphoma submitted to 18F-FDG PET/CT were retrospectively analyzed. The level
of significance was 5%. 18F-FDG cardiac uptake was assessed by three measurements: left ventricular maximum
standardized uptake value (SUVmax), heart to blood pool (aorta) ratio, and heart to liver ratio in all the exams.
Body weight, fasting blood sugar, post-injection time, and the injected dose of 18F-FDG between the scans were also
compared.
Results: Mean age was 50.4 ± 20.1 years and 50% was female. The analysis was carried out in two groups: baseline
vs. interim PET/CT, and baseline vs. post-therapy PET/CT. There was no significant difference in clinical variables or
protocol scans variables. We observed an increase in left ventricular (LV) SUVmax from 3.5±1.9 (baseline) to 5.6±4.0
(interim), p=0.01, and from 4.0±2.2 (baseline) to 6.1±4.2 (post-therapy), p<0.001. A percentage increase ≥30% of
LV SUVmax occurred in more than half of the sample. The rise of cardiac SUV was accompanied by an increase in LV
SUVmax/Aorta SUVmax and LV SUVmean/Liver SUVmean ratios.
Conclusion: This study showed a clear increase in cardiac 18F-FDG uptake in patients with lymphoma during and/or
after chemotherapy. The literature corroborates with these findings and suggests that 18F-FDG PET/CT is a sensitive
and reliable imaging exam to detect early metabolic signs of cardiotoxicity.

Full text

Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0
Original Article
Chemotherapy-induced Cardiac 18F-FDG Uptake in Patients with
Lymphoma: An Early Metabolic Index of Cardiotoxicity?
Mayara L. C. Dourado,1 Luca T. Dompieri,2 Glauber M. Leitão,³ Felipe A. Mourato,4 Renata G. G. Santos,4
Paulo J. Almeida Filho,4 Brivaldo Markman Filho,1 Marcelo D. T. Melo,5 Simone C. S. Brandão1
Departamento de Pós-Graduação em Ciências da Saúde, Universidade Federal de Pernambuco,1 Recife, PE – Brazil
Faculdade de Medicina, Universidade Federal de Pernambuco,2 Recife, PE – Brazil
Serviço de Oncologia, Hospital das Clínicas/Universidade Federal de Pernambuco,3 Recife, PE – Brazil
Real Nuclear, Real Hospital Português,4 Recife, PE – Brazil
Departamento de Medicina Interna, Universidade Federal da Paraíba,5 João Pessoa, PB – Brazil
Mailing Address: Simone Cristina Soares Brandão •
Departamento de Medicina Nuclear – Hospital das Clínicas – Universidade
Federal de Pernambuco – Rua Professor Moraes Rego, 1235.
Postal Code 50670-901, Recife, PE – Brasil
E-mail: sbrandaonuclearufpe@gmail.com
Manuscript received May 27, 2021, revised manuscript August 04, 2021,
accepted September 01, 2021
DOI: https://doi.org/10.36660/abc.20210463
Abstract
Background: It is uncertain whether myocardial fluorodeoxyglucose uptake occurs solely due to physiological features
or if it represents a metabolic disarrangement under chemotherapy.
Objective: To investigate the chemotherapy effects on the heart of patients with lymphoma by positron emission
tomography associated with computed tomography scans (PET/CT) with 2-deoxy-2[18F] fluoro-D-glucose (18F-FDG
PET/CT) before, during and/or after chemotherapy.
Methods: Seventy patients with lymphoma submitted to 18F-FDG PET/CT were retrospectively analyzed. The level
of significance was 5%. 18F-FDG cardiac uptake was assessed by three measurements: left ventricular maximum
standardized uptake value (SUVmax), heart to blood pool (aorta) ratio, and heart to liver ratio in all the exams.
Body weight, fasting blood sugar, post-injection time, and the injected dose of 18F-FDG between the scans were also
compared.
Results: Mean age was 50.4 ± 20.1 years and 50% was female. The analysis was carried out in two groups: baseline
vs. interim PET/CT, and baseline vs. post-therapy PET/CT. There was no significant difference in clinical variables or
protocol scans variables. We observed an increase in left ventricular (LV) SUVmax from 3.5±1.9 (baseline) to 5.6±4.0
(interim), p=0.01, and from 4.0±2.2 (baseline) to 6.1±4.2 (post-therapy), p<0.001. A percentage increase ≥30% of
LV SUVmax occurred in more than half of the sample. The rise of cardiac SUV was accompanied by an increase in LV
SUVmax/Aorta SUVmax and LV SUVmean/Liver SUVmean ratios.
Conclusion: This study showed a clear increase in cardiac 18F-FDG uptake in patients with lymphoma during and/or
after chemotherapy. The literature corroborates with these findings and suggests that 18F-FDG PET/CT is a sensitive
and reliable imaging exam to detect early metabolic signs of cardiotoxicity.
Keywords: Cardiotoxicity; Chemotherapy; Lymphoma.
Introduction
Chemotherapy and radiotherapy-induced cardiotoxicity
(CTX) encompasses various forms of injury to the cardiovascular
system, that trigger an increased production of reactive
oxygen (ROS) and nitrogen species, lipid peroxidation and
inflammation. This leads to cardiomyocyte apoptosis and
interstitial fibrosis, increasing the risk for impaired coronary
endothelial function, left ventricular (LV) dysfunction and
heart failure.1-3
Today, CTX is monitored by periodic imaging with
echocardiography for assessment of left ventricular
ejection fraction (LVEF) reduction and/or decreased global
longitudinal strain.4 However, the diagnosis of CTX based
on these cardiac function parameters is late, and can be
an indication of a significant and irreversible myocardial
injury.5,6 Therefore, it is necessary to evaluate myocardial
abnormalities at subcellular level for an early and sensitive
assessment of drug-induced CTX.7,8
Cardiac imaging techniques of nuclear medicine have
proved extremely useful to identify subclinical disease in
the context of cancer therapy-induced organ damage.9–11
Positron emission tomography associated with computed
tomography scans (PET/CT) with 2-deoxy-2[18F] fluoro-
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18F-FDG Uptake and Cardiotoxicity
D-glucose (18F-FDG) is widely used in oncology, especially
in patients with lymphoma.12,13 Tissue 18F-FDG uptake and
tissue distribution is variable and depend on several factors
such as glucose level, fasting period and drugs.14 Furthermore,
recent data suggest that myocardial 18F-FDG accumulation
is not entirely due to glucose consumption.15 The tracer
retention was found to be dependent upon the enzymatic
activity of hexose-6-phosphate-dehydrogenase (H6PD) in
the endoplasmic reticulum (ER).15 This enzyme can process
many hexoses, including FDG,16 to trigger a pentose phosphate
pathway and preserve NADPH levels in response to oxidative
stress conditions, such as CTX.17
This study aimed to identify potential early signs of
metabolic cardiac injury by assessing changes in cardiac
18F-FDG uptake by PET/CT in patients with lymphoma before,
during and/or after chemotherapy.
Material and Methods
Patients
Seventy patients diagnosed with lymphoma and submitted
to 18F-FDG PET/CT in the Division of Nuclear Medicine of Real
Hospital Português in Recife, Pernambuco, Brazil, between
January 1, 2012 and August 28, 2017 were retrospectively
analyzed in this study. The study was approved by the Research
Ethics Board of the Federal University of Pernambuco Health
Sciences Center, which granted a waiver of written consent
due to the retrospective nature of the study.
Inclusion criteria were primary diagnosis of lymphoma,
aged 10 years or older and, at least two 18F-FDG PET/CT scans
before, during and/or after chemotherapy. Exclusion criteria
were no baseline or control tests, unavailability and/or inability
to assess clinical data and imaging tests, and insulin therapy
on the day of the scan.
Patients’ clinical features, medical history and variables
related to the 18F-FDG PET/CT protocol recorded in their
medical records were collected, such as, weight, injected
dose of 18F-FDG, fasting blood sugar (FBS) and time after
injection. For imaging exams, 18F-FDG uptake was quantified
by measuring the mean and the maximum standardized
uptake value (SUVmean and SUVmax, respectively).
Four patients had only baseline and interim PET/CT scans,
40 had only baseline and post-therapy and 26 had all three.
For analysis, the patients were then divided into two groups,
group 1, patients with baseline and interim PET/CT scan data
(n = 30); and group 2, patients with baseline and post-therapy
PET/CT data (n = 66). Thus, some patients participated in
both analyses.
Each group was then divided in two subgroups according
to the change in the LV 18F-FDG SUVmax between baseline
and control tests: a percentage increase above or equal to
30% (Group ≥ 30%), and a less than 30% 18F-FDG uptake
change (Group <30%). The choice of a 30% cutoff was
based on PERCIST18 (PET Response Criteria in Solid Tumors),
which is a set of criteria for assessment of tumor response to
chemotherapy and radiotherapy, through metabolic changes
verified by 18F-FDG PET/CT scans.18
18F-FDG PET/CT Protocol
For the 18F-FDG PET/CT, patients were instructed to fast
at least six hours prior to the test, not to discontinue any
medication or exercise for 24 hours before the scan. On the
day of the scan, body weight (kg) and FBS were measured
and, venous puncture was used to administer 18F-FDG. Blood
sugar levels should be below 180 mg/dL. The 18F-FDG was
administered at an activity dose of 3.7 to 4.8MBq/kg and
after 60 minutes, the images were obtained by the PET/CT
(Biograph 16, Siemens Healthcare, USA), extending from the
base of the skull to the proximal-middle third of the femur,
three minutes per bed position. The acquisition parameters
of the CT scan included: 5mm slices, 120kV voltage, and no
intravenous contrast administration.
Imaging processing was done with iterative reconstruction
(two iteractions, eight subsets with Gaussian filter) by a
nuclear physician, who performed a quantitative analysis
with SUVmax and SUVmean. Both SUVs were measured at
the left ventricle on fused PET/CT images and determined
semi-automatically with the aid of the syngo via software
version 5.1 (Siemens Healthcare) through the demarcation of
a volume of interest (VOI) including the entire left ventricle.
SUVmax and SUVmean for blood pool were measured by
reconstruction of a region of interest (ROI) in the descendent
aorta just after the aortic arch. SUVmax and SUVmean for
liver were measured by reconstruction of a ROI of 4.0 cm
diameter in the VI segment.
Statistical analysis
Data was analyzed with Stata 12.1 statistical software.
Continuous variables were expressed as mean ± standard
deviation (SD); and categorical variables were summarized
by frequency and percentage. Percentage comparisons
between two independent groups were performed using the
Pearson’s chi-square test or, when it was not applicable, the
Fisher’s exact test. The Student’s t-test was used to compare
two means for both independent and paired samples. In
all tests, a significance level of 5% was used to reject the
null hypothesis.
Results
The mean age of the 70 patients studied was 50.4 ± 20.1
years (16-88 years) and 50% were female. Twenty patients
(28.6%) had hypertension and 10 (14.3%) had diabetes. About
67% (n= 47) had non-Hodgkin’s lymphoma (nHL) and the
remainder (n=23) had Hodgkin’s lymphoma (HL). Only three
patients (4.3%) underwent mediastinal radiotherapy between
the end of chemotherapy and the control 18F-FDG PET/CT
scan. It was possible to define the chemotherapy regimen
in 33 patients (47.1%) and all regimens included known
cardiotoxic drugs (Table 1).
Group 1: baseline and interim 18F-FDG PET/CT
There was standardization of the 18F-FDG PET/CT protocol
between the baseline and interim scans. There was no
difference in the injected dose of 18F-FDG, FBS and time
post-injection between baseline and interim exams. Mean
body weight of patients also did not change significantly,
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Table 1 – Clinical and therapeutic characteristics of the patients (n=70)
Variable N (%)
Female sex 35 (50.0)
Hypertension 20 (28.6)
Diabetes 10 (14.3)
Dyslipidemia 14 (20.0)
Smoking
Non-smoker 49 (70.0)
Former smoker 20 (28.6)
Current smoker 1 (1.4)
Alcoholism 0 (0)
Coronary artery disease 5 (7.1)
Hemodialysis 1 (1.4)
Medication
No 10 (14.3)
Non-cardioprotective medication a40 (57.1)
Cardioprotective medication a20 (28.6)
Cancer
Hodgkin’s Lymphoma 23 (32.9)
Non-Hodgkin’s Lymphoma 47 (67.1)
Chemotherapy b
RCHOP 11 (33.3)
RCHOP + alternative 6 (18.2)
ABVD 11 (33.3)
ABVD + alternative 2 (6.1)
DA-EPOCH-R 1 (3.0)
BEACOPP 1 (3.0)
RCOP 1 (3.0)
Mediastinal
Radiotherapy After Baseline Pet 3 (4.3)
a Cardioprotective medication: angiotensin II receptor blocker, beta-blocker, angiotensin-converting enzyme inhibitor. b Available for 33 patients. ABVD:
Adriamycin or Doxorubicin + Bleomycin + Vinblastine + Dacarbazine; BEACOPP: Bleomycin + Etoposide + Adriamycin or Doxorubicin + Cyclophosphamide
+ Vincristine + Procarbazine + Prednisolone; DA-EPOCH-R: Dose-Adjusted Etoposide + Prednisolone + Vincristine + Cyclophosphamide + Doxorubicin
or Hydroxydaunorubicin + Rituximab, RCHOP: Rituximab + Cyclophosphamide + Doxorubicin or Hydroxydaunorubicin + Vincristine + Prednisolone,
RCOP: Rituximab + Cyclophosphamide + Vincristine + Prednisolone.
making it possible to compare the 18F-FDG uptake in the
target organs (Table 2).
On the other hand, 18F-FDG LV SUVmax increased at
the interim scan compared to baseline. Similarly, there was
a significant increase in the LV SUVmax/aorta SUVmax and
LV SUVmean/liver SUVmean ratios from baseline to interim
scans (Figure 1A). The mean time interval between baseline
and interim scans was 95.4 ± 32.2 days.
Of the 30 patients who underwent baseline and interim
18F-FDG PET/CT scans,16 (53.3%) presented an increase
≥30% (Group ≥ 30%) in 18F-FDG LV SUVmax. Regarding
clinical variables, such as cardiovascular risk factors and drugs
in use, no differences were observed.
The values of the LV SUVmax/aorta SUVmax and LV
SUVmean/liver SUVmean ratios also increased significantly at
the interim evaluation compared to the baseline in the group
≥30% (Figure 1B). In the group<30% (n=14), there was no
statistically significant increase in these ratios from baseline
to interim scans (Figure 1C).
Group 2: baseline and post-therapy 18F-FDG PET/CT
Sixty-six patients underwent baseline and post-therapy
18F-FDG PET/CT scans. No statistically significant differences
were seen in FBS, 18F-FDG injected activity and time post-
injection were found between the two evaluations. Patients’
mean body weight was slightly higher in the post-therapy scan
compared with baseline (Table 3).
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Table 2 – Comparison of body weight, fasting blood sugar, injected dose of 18F-fluorodeoxy glucose (18FDG), and mean
post-injection time of patients between baseline and interim positron emission tomography associated with computed tomography
(PET/CT) scans
Variable (N=30) Baseline Interim p*
Mean ± SD Mean ± SD
Weight (Kg) 75.3 ± 14.3 74.7 ± 13.5 0.551
FBS (mg/dL) 92.6 ± 19.5 93.4 ± 19.9 0.816
Dose of 18FDG mCi 9.1 ± 2.7 9.1 ± 2.0 0.971
Post-injection time (min) 68.8 ± 10.0 65.9 ± 9.9 0.308
*Student’s t-test. FBS: Fasting Blood Sugar
Figure 1 – Group 01 – A) Comparison of maximum left ventricular (LV) standardized uptake value (SUVmax), LV SUVmax/aorta SUVmax and mean LV SUV
(SUV mean)/liver SUVmean ratios, between baseline and interim positron emission tomography (PET). B) Comparison of LV SUVmax/aorta SUVmax and LV
SUVmean/liver SUVmean ratios between baseline and interim PET in the Group with increase of LV SUVmax ≥ 30%. C) Comparison of LV SUVmax/Aorta
SUVmax and LV SUVmean/Liver SUVmean ratios, between Baseline and Interim PET in the Group with increase of LV SUVmax < 30%; LVmaxAOmax: LV
SUVmax/Aorta SUVmax, LVmean LIVER mean: LV SUVmean/Liver SUVmean.
The mean value of the LV SUVmax was significantly higher
in the post-therapy PET. We observed an absolute increase
in the 18F-FDG cardiac uptake value of 2.1 (95% CI:1.3
to 3.0), which represents a percentage increase of 66.5%
(95%CI:43.3% to 89.7%) over the baseline scan.
The values of the LV SUV max/aorta SUV max and the LV SUV
mean/liver SUV mean ratios also increased significantly in the post-
therapy PET as compared with baseline, Figure 2A. The mean time
between baseline and post-therapy exams was 231.8±125.7 days.
Of the 66 patients, 38 (57.6%) presented ≥30% increase
in 18F-FDG cardiac uptake (Group ≥ 30%). There were no
differences between the groups regarding the clinical variables,
such as cardiovascular risk factors and medications in use.
The values of the LV SUVmax/aorta SUVmax and LV
SUVmean/liver SUVmean ratios increased significantly in
the post-therapy evaluation compared to the baseline in the
≥30% group (Figure 2B). In the Group<30% (n=28), there
was no statistically significant increase in the ratios (Figure 2C).
Figure 3 illustrates a case example of the 18F-FDG LV SUV
max behavior before, during and after chemotherapy.
Discussion
The present study showed that chemotherapy in patients
with lymphoma caused an unbalance in cardiac metabolism,
evidenced by a higher myocardial 18F-FDG uptake. These
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Table 3 – Comparison of body weight, fasting blood sugar, injected dose of 18F-fluorodeoxy-glucose (18FDG), and mean post-injection
timel of patients between baseline and post-therapy positron emission tomography associated with computed tomography scans
(PET/CT)
Variable (N=66) Baseline Pet Post-Therapy Pet p*
Mean ± SD Mean ± SD
Weight (Kg) 72.7 ± 14.8 75.2 ± 15.2 0.014
FBS (mg/dL) 91.6 ± 15.6 91.6 ± 16.7 >0.99
Dose of 18FDG mCi 9.2 ± 2.3 9.5 ± 2.2 0.308
Post-injection time (min) 68.6 ± 9.1 70.4 ± 5.8 0.606
*Student’s t-test. FBS: Fasting Blood Sugar
Figure 2 – Group 02 – A) Comparison of LV SU Vmax, LV SUVmax/Aorta SUVmax and LV SUVmean/Liver SUVmean ratios, between Baseline and Post-therapy
PET. B) Comparison of LV SUVmax/Aorta SUVmax and LV SUVmean/Liver SUVmean ratios, between Baseline and Post-therapy PET in the Group with
increase of LV SUVmax ≥ 30%. C) Comparison of LV SUVmax/Aorta SUVmax and LV SUVmean/Liver SUVmean ratios, between Baseline and Post-therapy
PET in the Group with increase of LV SUVmax < 30%; LVmaxAOmax: LV SUVmax/Aor ta SUVmax, LVmean LIVER mean: LV SUVmean/Liver SUVmean.
Figure 3 – Case example - LV SUVmax in Baseline (5.86), Interim (8.95 / 52.73% percentage increase from baseline) and Post-therapy PET/CT (9.67 /
65.02% percentage increase from baseline). LV: Left Ventricle; PET/CT: Positron emission tomography associated with computed tomography scans; SUV:
Standard Uptake Value; SUVmax: Maximum SUV.
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results are supported by recent evidence suggesting that it may
be an early sign of CTX in response to the redox stress. The
cardiac 18F-FDG increase occurred in more than 50% of the
patients and was observed in the interim PET and in the post-
therapy scan. These results suffered no interference regarding
the18F-FDG injected activity or any possible differences in
exam preparation and timing.
The 18F-FDG PET/CT is a well-established method in
the diagnosis and staging of oncologic patients, especially
with lymphoma, with a potential capacity to assess early
manifestations of CTX in a way analogue to the ischemic
cascade, as postulated in Figure 4.
Antineoplastic therapies have improved overall survival
rates in oncologic patients. However, their cytotoxic
effects have shown a wide spectrum of acute and chronic
alterations to the cardiovascular system.19 The cellular and
molecular mechanisms of CTX are known to disrupt the redox
homeostasis mostly in the myocardium and endothelium,
significantly impairing cardiovascular health.20
CTX affects the cardiovascular system first by the inhibition
of topoisomerase II and the formation of ROS. The intrinsic
mitochondria-dependent and extrinsic death receptor
pathways of apoptosis are then triggered. The cascade
continues with the activation of caspase 3, phosphatidylserine
expression, DNA fragmentation, chromatin condensation,
and phospholipid membrane metabolization.21 The final
stage is characterized by membrane blebbing and cell
shrinkage.22 This is the mechanism underlying subclinical
CTX and it provides various opportunities to assess early
signs of this entity.
The current recommendations and guidelines rely on
imaging techniques focused on anatomy-based parameters,
such as echocardiography, multigated radionuclide angiography
(MUGA), and cardiac magnetic resonance imaging (CMRI).23
However, these approaches detect late manifestations of CTX
with low sensitivity for subclinical alterations.24
Nuclear medicine techniques may be a tool to assess
specific points of the CTX pathway. The 18F-FDG PET/CT,
commonly used to detect tumoral glycolytic metabolism, has
presented itself as an early marker of CTX. Initially, several
studies pointed out that doxorubicin (DXR), one of the most
utilized anthracyclines, can specifically affect myocardial
metabolism, as showed by experimental study.25
Several experimental and clinical studies have shown that
cardiotoxic therapy, such as sunitinib and anthracyclines,
increases the cardiac 18F-FDG uptake over time and is related
to echocardiographic alterations.26-33
Although 18F-FDG uptake has been commonly associated
with glucose consumption, more recent data have shown
otherwise. The redox stress and its antioxidant response
have been characterized as a possible mechanism behind
the progression of cardiac contractile impairment in CTX
and in the 18F-FDG uptake independently of the glycolytic
metabolism.34
Redox stress to the endoplasmic reticulum (ER) environment
might activate the local H6PD-triggered pentose phosphate
pathway to fuel the NADPH levels needed for the antioxidant
response, and is related to an increased 18F-FDG uptake.35
In situations of oxidative stress, NADPH is a major source of
electrons for reductive reactions.36 It is generated intraluminally
by H6PD, a bifunctional enzyme that catalyzes the first two
steps of the pentose phosphate pathway, converting glucose-
6-phosphate to 6-phosphogluconate with the concomitant
production of NADPH.37 H6PD has as substrate several
hexoses such as 2-deoxyglucose and FDG.38
In the heart, there is a direct link between ER oxidative
stress and myocardial uptake of 2-deoxyglucose,39 that may be
considered an early metabolic phase of contractile dysfunction
by pressure overload.40 Furthermore, Hrelia et al.41 showed
that the increase of 2-deoxyglucose uptake induced by DXR
in cardiomyocytes can be reverted by the antioxidant effect
of alpha-tocopherol.41
Bauckneht et al.,33 in 2019, analyzed the effect of DXR
-induced oxidative damage on the correlation between
myocardial 18F-FDG uptake, overall glucose consumption and
the H6PD-triggered metabolic response in mice. The study
showed that myocardial redox stress persisted and directly
correlated with the enhancement in 18F-FDG uptake (SUV
increase), and the activation of physiological antioxidant
pathways such as the catalytic function of H6PD.33 The study
also showed that the metabolic alteration persisted after the
disappearance of DXR, and it preceded the manifestation
of contractile impairment.33 Previous reports also showed a
positive loop connecting ROS generation and 18F-FDG uptake
in cancer.42
In agreement with these findings, recent studies showed an
increased 18F-FDG uptake on PET/CT independent of glycolytic
metabolism and linked to the enzymatic activity of H6PD in
the brain.43,44 Another analysis showed the link between 18F-
FDG uptake and ROS generation in hyperglycemia-induced
redox stress involving H6PD activation.45
Despite its interesting results and background of the
present study, its retrospective nature makes the assessment
of the mechanisms underlying the increased myocardial 18F-
FDG uptake difficult. However, no other cardiotoxic factors,
besides CTX, were identified between baseline and control
exams in the largest sample of patients with lymphoma
evaluated during and after chemotherapy. In addition, unlike
the other studies, we measured not only the LV SUVmax, but
also the LV uptake values corrected for liver and blood pool,
as control, confirming the increase of the cardiac uptake.
Furthermore, the 18F-FDG PET/CT protocol and the possible
factors of SUV variability were the same in all baseline and
control scans.
More studies are necessary to correlate increased cardiac
18F-FDG uptake with clinical outcomes, the class and dose
of chemotherapy, troponin and NT-proBNP levels, and with
other imaging methods such as echocardiography and CMRI.
Conclusion
The present study showed a clear increase in cardiac
18F-FDG uptake in patients with lymphoma, verified by
18F-FDG PET/CT during and/or after chemotherapy. The
literature corroborates with these findings and suggests that it
may be an important and early sign of CTX that can be easily
assessed by a widely available method. With the progressive
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18F-FDG Uptake and Cardiotoxicity
Figure 4 – Cardiotoxicity cascade – Cardiotoxic injury triggers series of metabolic alterations in response to the oxidative stress, it is detectable by 18F-FDG
PET/CT. The sustained injury and the failure of the myocyte self-healing contribute to cell dysfunction and mechanic alterations detected by strain rate
imaging. Furthermore, the process continues with a decrease in the cardiac overall performance assessed by the LVEF. Signs of heart failure are then
noticeable, suggesting that the heart no longer meet the body’s demands, or do it at the expense of high ventricular filling pressures (ROS: reactive oxygen
species; ER: endoplasmic reticulum; PPP: pentose phosphate pathway; H6PD: hexose-6-phosphate dehydrogenase; FDG: 18F-fluorodeoxy-glucose; LVEF:
Left Ventricle Ejection Fraction).
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improvement in anticancer therapies, CTX is still a concern that
requires further investigation and new diagnostic approaches.
Acknowledgements
We are pleased to acknowledge the support provided by
all technicians and nuclear physicians of the Real Nuclear at
the Real Hospital Português in hosting our study.
Author Contributions
Conception and design of the research: Dourado MLC,
Leitão GM, Mourato FA, Almeida Filho PJ, Markman Filho
B, Melo MDT, Brandão SCS; Acquisition of data, Analysis
and interpretation of the data and Critical revision of the
manuscript for intellectual content: Dourado MLC, Dompieri
LT, Leitão GM, Mourato FA, Santos RGG, Almeida Filho PJ,
Markman Filho B, Melo MDT, Brandão SCS; Statistical analysis:
Dourado MLC, Brandão SCS; Obtaining financing: Dourado
MLC; Writing of the manuscript: Dourado MLC, Dompieri
LT, Brandão SCS.
Potential Conflict of Interest
No potential conflict of interest relevant to this article was
reported.
Sources of Funding
There were no external funding sources for this study.
Study Association
This article is part of the thesis of master submitted
by Mayara L. C. Dourado, from Universidade Federal de
Pernambuco - UFPE.
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Original Article
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18F-FDG Uptake and Cardiotoxicity
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