Original Article
Semiquantitative evaluation of 68Ga-DOTANOC uptake in the normal myocardium: establishment of reference values

https://doi.org/10.1007/s12350-022-03135-wGet rights and content

Abstract

Background

To ascertain presence of physiological uptake and derive standardized uptake values (SUV) of 68Ga-DOTANOC in normal myocardium and establish reference values.

Methods and results

Dedicated cardiac 68Ga-DOTANOC PET/CT studies of patients referred for evaluation of cardiac sarcoidosis (CS) or myocarditis and found to be normal on visual assessment and on cardiac MRI were analyzed semiquantitatively. The studies were acquired 45-60 minutes after intravenous injection of 111-185 MBq of 68Ga-DOTANOC. Myocardial SUVmax normalized to lean body mass (SUVmax_lbm) values for septum, anterior wall, proximal lateral wall, distal lateral wall, inferior wall, and apical region were 1.12 ± .39, 1.09 ± .42, 1.26 ± .49, 1.16 ± .40, 1.23 ± .39, and 1.05 ± .40, respectively. Myocardial SUVmax_lbm-to-blood pool SUVmean_lbm ratios were calculated for each region and 95th percentile values of these ratios were considered the upper limit of normal. 95th percentile values of myocardial SUVmax_lbm-to-blood pool SUVmean_lbm ratio for the corresponding regions were 1.70, 1.70, 2.00 1.95, 2.05, and 1.70, respectively.

Conclusion

There can be physiological uptake of 68Ga-DOTANOC in normal myocardium and the reference values of semiquantitative parameters established in this study may be employed as a corroborative tool for visual assessment in patients undergoing 68Ga-DOTANOC PET/CT for suspected CS or myocarditis.

Introduction

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography computed tomography (PET/CT) is a standard imaging modality for detecting inflammation by virtue of its ability to demonstrate high glucose metabolism in activated leucocytes at the sites of inflammation. 18F-FDG is transported into the inflammatory cells by glucose transporters (GLUT 1 and 3) and converted to 18F-FDG-6-phosphate by hexokinase but unlike glucose, it is not metabolized further. The degree of uptake is proportional to the metabolic rate of cells and the expression of GLUT transporters. Inflammatory cells show a high rate of glycolysis during the ‘respiratory burst,’ as well as increased expression of GLUT transporters and an increased affinity for deoxyglucose mediated by various pro-inflammatory cytokines. It is a readily available radiotracer and allows sensitive high-resolution tomographic imaging for inflammation.1 However, it has limitations in detecting inflammation in the myocardium due to the high physiological uptake in the normal myocardium. Although various methods are recommended to suppress this physiological uptake, such as prolonged fasting, high fat low carbohydrate diet, and use of heparin, a significant proportion of patients fail to achieve adequate suppression making it difficult to interpret 18F-FDG PET/CT cardiac study in patients with suspected cardiac sarcoidosis (CS) or myocarditis.2

Somatostatin receptor (SSTR) imaging using PET tracers such as 68Ga-labeled DOTANOC, DOTATOC, and DOTATATE is an emerging modality for detecting myocardial inflammation as SSTRs are highly expressed in activated macrophages and lymphocytes. Although SSTR expression has been demonstrated in the normal myocardium in molecular studies, it has been reported that no significant physiological uptake of 68Ga-DOTANOC is seen in the myocardium.3 Recent studies have demonstrated the utility of 68Ga-DOTANOC in CS.4, 5, 6 Moreover, SSTR subtype 2 expression has been immunohistochemically demonstrated to be specific for cells undergoing epithelioid transformation and on giant cells.7 Thus, imaging using 68Ga-DOTANOC which has a high affinity for SSTR subtype 2 and 5 makes it a useful tool in detecting myocardial inflammation.

Semiquantitative evaluation with PET/CT using standardized uptake value (SUV) and SUV-based metrics may offer greater diagnostic accuracy and has been used for 18F-FDG PET/CT in CS for diagnosis, prognosis, and predicting response to immunosuppressive treatment.8, 9, 10 A similar approach can therefore be employed for 68Ga-DOTANOC PET/CT, especially when the visual analysis is equivocal. A knowledge of SUV values in normal myocardium thus becomes imperative for such assessment.

The aim of this study is to evaluate semiquantitatively the uptake of 68Ga-DOTANOC in the normal myocardium and establish the reference values which might supplement visual analysis as a corroborative parameter, especially in situations where the visual analysis is doubtful or equivocal.

Section snippets

Materials and methods

This study had an observational descriptive cross-sectional design. The Institutional Ethics Committee approved the study (IEC No. IECPG-194/23.08.2017, RT-25/07.09.2017). Due to the retrospective nature of the study, the requirement for informed written consent was waived.

Results

A total of 128 negative 68Ga-DOTANOC cardiac PET/CT studies were screened and 79 patients (53 male and 26 female) were finally included in the study. The reasons for exclusion are outlined in Figure 1. The median age was 42 years (range 15-73). All were referred for evaluation of suspected CS or myocarditis. Cardiac MRI as well as 68Ga-DOTANOC PET/CT (on visual analysis) were negative for cardiac sarcoidosis or myocarditis in all. The duration between PET/CT and cardiac MRI was ≤ 2 weeks.

Out of

Discussion

SSTR targeting PET radiotracers such as 68Ga-labeled DOTANOC, DOTATOC, and DOTATATE have potential as promising agents for imaging myocardial inflammation as they do not show significant physiological uptake in the normal myocardium. Although 68Ga-DOTANOC has high affinity for both SSTR subtypes 2 and 5, it has been reported that the normal myocardium does not show any significant uptake of this tracer extent, whereas some physiological uptake in the myocardium has been observed with 68

New Knowledge Gained

This study describes semiquantitatively the uptake of 68Ga-DOTANOC in the normal myocardium in terms of region-wise myocardial SUVmax_lbm values and myocardial SUVmax_lbm-to-blood pool SUVmean_lbm ratio using dedicated cardiac PET/CT studies which has not previously been described in literature. The reference values thus determined can supplement visual analysis of 68Ga-DOTANOC cardiac PET/CT.

Conclusion

There can be physiological uptake of 68Ga-DOTANOC in the normal myocardium. Semiquantitative evaluation may be employed as a corroborative tool for visual assessment in patients undergoing 68Ga-DOTANOC PET/CT for suspected CS or myocarditis especially when the visual assessment is equivocal. The reference uptake values determined in our study can guide a more thorough approach to interpreting dedicated cardiac 68Ga-DOTANOC PET/CT studies in patients with suspected CS or myocarditis, for

Disclosures

Prateek Kaushik, Chetan Patel, Khangembam Bangkim Chandra, Suraj Kumar, Priyanka Gupta, Vineeta Ojha, and Chandrasekhar Bal have no conflicts of interest to declare.

Funding

The authors did not receive any funding for this work.

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