PET imaging of pheochromocytoma and paraganglioma - 18F-FDOPA vs. somatostatin analogues

Context: Functional imaging with positron emission tomography (PET) scans is an essential part of the diagnostic workup for pheochromocytoma and paraganglioma (PPGL). The purpose of this review is a) to provide a brief overview of functional imaging for PPGL, b) summarize selected present and older guideline and review recommendations, and c) conduct a literature review on the diagnostic performance of the most used PET tracers for PPGL.

Evidence acquisition: We conducted a systematic literature search in PubMed from January 2004 to August 2024 with the search string: ("Pheochromocytoma" OR "Paraganglioma") AND ("Positron-Emission Tomography" OR "Radionuclide Imaging" OR ("PET" AND ("FDG" OR "DOTATOC" OR "DOTANOC" OR "DOTATATE" OR "DOPA" OR "FDOPA"))). Studies involving PET scans of at least 20 individuals with PPGL, or at least five individuals in a rare, well-defined subgroup of PPGL (e.g. sympathetic or head-neck paragangliomas, and specific pathogenic variants) were included.

Evidence synthesis: Seventy studies were identified of which 21 were head-to-head comparisons of at least two different PET tracers (18F-fluorodihydroxyphenylalanine, 18F-FDOPA; 68Ga-DOTA-conjugated somatostatin analogues, 68Ga-SSA; and 18F-fluorodeoxyglucose, 18F-FDG). 18F-FDOPA had higher sensitivity for pheochromocytoma compared to 68Ga-SSA and equal sensitivity for metastatic pheochromocytoma. 18F-FDOPA and 68Ga-SSA had similar sensitivity for primary non-SDHx sympathetic and head-neck paraganglioma. However, 68Ga-SSA had higher sensitivity for metastatic sympathetic and head-neck paraganglioma and for SDHx-related paraganglioma.

Conclusion: 18F-FDOPA and 68Ga-SSA PET are both sensitive for localizing PPGL. However, 18F-FDOPA is the most sensitive for detecting pheochromocytoma, while 68Ga-SSA is superior to 18F-FDOPA for metastatic sympathetic and head-neck paraganglioma and SDHx-related paraganglioma.