Pre-therapy functional imaging as a tool for personalized treatment selection in pheochromocytoma and paraganglioma: A theranostic perspective

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous biological behavior, requiring individualized diagnostic and therapeutic strategies. This review aimed to evaluate the role of functional imaging, particularly [^123I]I-MIBG scintigraphy and [^68Ga]Ga-DOTATATE PET/CT, in guiding personalized treatment selection within a theranostic framework. A comprehensive literature review was performed using PubMed and other scientific databases, including clinical studies, systematic reviews, retrospective analyses, and international guidelines. The analysis focused on diagnostic performance, molecular imaging characteristics, genotype–phenotype associations, tumor heterogeneity, and the impact of imaging findings on radionuclide therapy selection. [^68Ga]Ga-DOTATATE PET/CT demonstrated superior sensitivity, especially in metastatic PPGLs and SDHB-associated disease, and enabled identification of patients potentially eligible for peptide receptor radionuclide therapy (PRRT). Although less sensitive, [^123I]I-MIBG scintigraphy remains essential for selecting candidates for [^131I]I-MIBG therapy. Functional imaging revealed substantial interlesional heterogeneity, reflecting differences in receptor expression and tumor biology that may influence treatment response. Functional imaging is a fundamental component of precision management in PPGLs. The integration of molecular imaging with therapeutic radionuclide approaches enables identification of the predominant molecular target and supports individualized treatment decisions. MIBG scintigraphy and [^68Ga]Ga-DOTATATE PET/CT should be considered complementary modalities within a comprehensive theranostic strategy.