Comparison of three interpretation criteria for [⁶⁸Ga]Ga-DOTATATE PET/CT in suspected pheochromocytoma and paraganglioma of the adrenal gland or retroperitoneal space

Pheochromocytomas and paragangliomas (PPGLs) frequently overexpress somatostatin receptor subtype 2 (SSTR2), making [ 68 Ga]Ga-DOTATATE PET/CT a promising functional imaging modality. However, the optimal interpretation criteria for distinguishing PPGL from non-PPGL lesions in clinically suspected adrenal or retroperitoneal masses remain undefined. This retrospective study evaluated the diagnostic performance of [⁶⁸Ga]Ga-DOTATATE PET/CT by systematically comparing three interpretation criteria: Integrated Interpretation (combining PET/CT metabolic patterns, CT morphology, and clinical information), Liver Threshold Interpretation (lesion SUV max ≥ liver SUV mean ), and Blood-Pool Threshold Interpretation (lesion SUV max ≥ 5 × blood-pool SUV mean ). Thirty-six patients with suspected adrenal or retroperitoneal PPGL underwent [ 68 Ga]Ga-DOTATATE PET/CT; all target lesions were histopathologically confirmed. Sensitivity, specificity, accuracy, and ROC analyses were performed. Histopathology confirmed PPGL in 22 patients (18 adrenal, 4 extra-adrenal) and non-PPGL in 14 patients. The Liver Threshold Interpretation achieved 100% sensitivity (22/22), 78.6% specificity (11/14), and 91.7% accuracy (33/36), significantly outperforming the Integrated Interpretation in sensitivity (100% vs. 77.3%, P = 0.018), negative predictive value (100% vs. 70.6%, P = 0.047), and accuracy (91.7% vs. 80.6%, P < 0.001). The AUC of Liver Threshold (0.893) was significantly larger than those of Integrated (0.815, P = 0.042) and Blood-Pool (0.714, P = 0.014). Optimal cutoffs were SUV max ≥ 6.95 (AUC 0.893) and lesion-to-liver ratio ≥ 0.95 (AUC 0.893). PPGL lesions showed higher SUV max (24.4 ± 19.1 vs. 5.3 ± 3.5, P = 0.001) and smaller volumes. The ‘target sign’ (ring-like peripheral uptake) was more frequent in PPGLs (45.5% vs. 7.1%, P = 0.025). [ 68 Ga]Ga-DOTATATE PET/CT demonstrates high diagnostic accuracy in distinguishing PPGL from non-PPGL lesions in clinically suspected adrenal or retroperitoneal masses. The Liver Threshold Interpretation is a practical screening tool with 100% sensitivity and 91.7% accuracy. Optimal semiquantitative cutoffs (lesion SUV max ≥ 6.95 or lesion-to-liver ratio ≥ 0.95) provide reliable discrimination.