Head-to-head comparison between [68Ga]Ga-DOTA-NOC and [18F]DOPA PET/CT in a diverse cohort of patients with pheochromocytomas and paragangliomas

Purpose To compare the detection ability of Ga-68-labelled DOTA-l-Nal3-octreotide ([Ga-68]Ga-DOTA-NOC) and 6-[F-18]fluoro-L-3,4-dihydroxyphenylalanine ([F-18]DOPA) in patients with phaeochromocytomas and paragangliomas (PPGLs) of different origins and gene mutations, such as germline succinate dehydrogenase complex genes (SDHx). Methods Eighty-five patients with histopathologically confirmed PPGLs who underwent both [Ga-68]Ga-DOTA-NOC and [F-18]DOPA PET/CT from March 2017 to June 2023 were enrolled in this retrospective study. For comparative analyses, PPGLs were classified as phaeochromocytoma (PCC), sympathetic paraganglioma (sPGL), and head/neck paraganglioma (HNPGL). Detection rates were analyzed on per-patient and per-lesion bases and compared using the Chi-square/Fischer's exact test. Results Among 85 patients with PPGLs (48 males; 43 years +/- 17 [SD]), the patient-based detection rates of [Ga-68]Ga-DOTA-NOC and [F-18]DOPA PET/CT were 87.1% (74/85) and 89.4% (76/85), respectively (p = 0.634), and the lesion-based detection rates were 80.8% (479/593) and 71.2% (422/593), respectively (p < 0.001). Only one patient with a recurrent PCC presented double-negative imaging, while 66 patients exhibited double-positive imaging. The remaining patients were either [Ga-68]Ga-DOTA-NOC-negative/[F-18]DOPA-positive (n = 10) or [Ga-68]Ga-DOTA-NOC-positive/[F-18]DOPA-negative (n = 8). In subgroup analyses, [Ga-68]Ga-DOTA-NOC PET/CT detected significantly more metastases of sPGL (91.1%, 236/259) and SDHx-related PPGL (89.6%, 86/96) than [F-18]DOPA PET/CT (48.6%[126/259] and 50.0%[48/96], respectively; both p < 0.001). However, [F-18]DOPA showed significantly higher detection rates of PCC in both primary/recurrent and metastatic lesions (94.3%[50/53] vs. 62.3%[33/53] and 87.9%[174/198] vs. 69.2%[137/198], respectively; both p < 0.001). Regarding metastases in different organs, [Ga-68]Ga-DOTA-NOC PET/CT detected more lesions than [F-18]DOPA PET/CT in bone (96.2%[176/183] vs. 66.1%[121/183]; p < 0.001) and lymph nodes (82.0%[73/89] vs. 53.9%[48/89]; p < 0.001) but less lesions in peritoneum (20%[4/20] vs. 100%[20/20]; p < 0.001). Conclusion [Ga-68]Ga-DOTA-NOC and [F-18]DOPA are complementary in diagnosing PPGL under the appropriate clinical setting. [Ga-68]Ga-DOTA-NOC should be considered as the ideal first-line tracer for detecting metastases of sPGL and SDHx-related tumours, whereas [F-18]DOPA may be the optimal tracer for evaluating non-SDHx-related PCC, especially in detecting primary lesions and monitoring recurrence.