[68Ga]Ga-DOTATATE uptake in pheochromocytoma/paraganglioma predicts SSTR2 expression by immunohistochemistry: Strongest uptake in head and neck paraganglioma

Abstract Purpose Pheochromocytomas and paragangliomas (PPGLs) are endocrine tumors that may express somatostatin receptors (SSTRs). Importantly, SSTR2 expression is associated with metastatic behavior and succinate dehydrogenase B ( SDHB ) pathogenic variants. Somatostatin receptor analogue (SSA) positron emission tomography-computed tomography (PET/CT) is therefore widely used for diagnosis and localization of PPGLs, particularly in extra-adrenal, metastatic, or SDHB -related disease. This study aimed to evaluate whether cellular SSTR expression by immunohistochemistry (IHC) correlates with radionuclide uptake on SSA PET/CT and could serve as a biomarker for detectability on SSA imaging. Methods In 35 patients with PPGLs treated at the University Hospital Zurich, IHC for SSTR2 and SSTR5 was performed on tumor tissue samples and evaluated both manually and with digital image analysis (DIA). SSTR2 mRNA expression was determined by qRT-PCR. The association of SSTR expression at the cellular level and standardized uptake value (SUV) on [ 68 Ga]Ga-DOTATATE PET/CT was analyzed. Results IHC expression was assessed in 38 lesions. Manual and DIA quantification of IHC SSTR2 expression correlated strongly (r s 0.86; p  < 0.001). Manual SSTR2 expression correlated with both liver-corrected PET maximum SUV (SUV max ) (r s 0.53, p  = 0.001) and liver-corrected PET mean SUV (SUV mean ) (r s 0.48, p  = 0.002) of the corresponding lesion. SSTR2 expression by IHC was highest in head and neck paragangliomas (HNPGLs), with significantly higher SUV max and SUV mean compared to pheochromocytomas and abdominal paragangliomas. SSTR2 mRNA expression did not correlate with SSTR2 expression by IHC or PET metrics. Conclusions SSTR2 expression by IHC correlates with [ 68 Ga]Ga-DOTATATE uptake, with highest expression found in HNPGLs.