Quantitative analysis of 68Ga-DOTA(0)-Tyr(3)-octreotate positron emission tomography/computed tomography imaging for the differential diagnosis of primary pheochromocytoma and paraganglioma

Background: Pheochromocytomas/paragangliomas (PPGLs) predominantly express somatostatin receptors (SSTRs) 2 and 3. Ga-68-DOTA(0)-Tyr(3)-octreotate (Ga-68-DOTA-TATE) is an imaging radiopharmaceutical that selectively targets SSTR 2 with high affinity. The purpose of this study was to evaluate the utility of Ga-68-DOTA-TATE in the differential diagnosis of suspected PPGLs, and determine the optimal threshold for differential diagnoses. Methods: This retrospective study reviewed consecutive patients referred to the Chinese PLA General Hospital, Beijing between April 2018 and December 2020 who underwent both biochemical testing for catecholamine and Ga-68-DOTA-TATE positron emission tomography/computed tomography (PET/CT) for suspected PPGLs, without prior history. Patients with pathologic confirmation were selected for analysis. The following values were obtained for a quantitative analysis of Ga-68-DOTA-TATE imaging: maximal standardized uptake value (SUVmax), the ratio between the SUVmax of the lesion and the mean SUV (SUVmax) of the liver (SUVR), and the Krenning score (KS) of the lesion. According to their location, tumors were grouped as adrenal or extra-adrenal. Receiver operating characteristic (ROC) curves of the SUVR and KS were determined, and their diagnostic performance was calculated using general and subgroup-specific optimal thresholds. Concordance between the SUVR and KS was analyzed using a McNemar test. Results: A total of 38 patients with PPGLs and 21 with non-PPGLs tumors were included in the final analysis. When a general optimal threshold for adrenal tumors was applied in pheochromocytoma (PCC) diagnosis, the sensitivity, specificity, and accuracy of the SUVR and KS were 86.4% (19/22) and 90.9% (20/22), 92.9% (13/14) and 78.6% (11/14), and 88.9% (32/36) and 86.1% (31/36), respectively. The SUVR and KS diagnostic results showed no differences in paraganglioma (PGL) diagnosis, with a sensitivity, specificity, and accuracy of 43.8% (7/16), 100.0% (7/7), and 60.9% (14/23), respectively. Using PPGL-specific optimal thresholds improved the diagnostic accuracy for extra-adrenal tumors. The diagnostic results of the SUVR and KS showed high concordance in both general and subgroup analyses. When PPGL-specific optimal thresholds were used, Ga-68-DOTA-TATE PET/CT correctly diagnosed 1 PCC with negative biochemical test results, and 5 PCCs and 1 PGL with borderline biochemical test results. Conclusions: Applying PPGL-specific thresholds of Ga-68-DOTA-TATE in diagnosing adrenal and extra-adrenal tumors is recommended for the differential diagnosis of PPGLs. When biochemical tests are negative or borderline, Ga-68 DOTA TATE PET/CT should be included in the diagnostic procedure. The visual KS method has almost the same diagnostic efficiency as the quantitative SUVR method and has potential for recommendation in Ga-68-DOTA-TATE image analysis.