Future scenarios of radioligand therapy in pheochromocytomas and paragangliomas

Pheochromocytomas and paragangliomas (PPGL) are rare and heterogeneous neuroendocrine tumors for which therapeutic options remain limited, particularly in the metastatic or progressive setting. Radioligand therapy (RLT) has emerged as a promising strategy, leveraging tumor-specific molecular targets to deliver cytotoxic radiation.

This review provides a structured and updated overview of RLT in PPGL, critically comparing the two main therapeutic radiopharmaceuticals-[¹³¹I]mIBG and [¹⁷⁷Lu]Lu DOTATATE-and discussing their clinical evidence, safety profiles, patient selection criteria, and positioning within current guidelines. Emerging approaches, including alpha emitter-based therapies and novel theranostic targets, are also explored.

A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science (updated to August 2024), focusing on studies evaluating RLT in PPGL. Due to heterogeneity in study design, protocols, and outcome measures, a metaanalysis was not feasible.

Evidence derives predominantly from small retrospective studies and a limited number of prospective cohorts. Both [¹³¹ I]mIBG and [¹⁷⁷ Lu]LuDOTATATE demonstrate favorable safety profiles and high disease control rates, although with substantial variability in protocols and patient populations. Comparative analyses suggest longer progressionfree survival with PRRT in selected patients, particularly those with high somatostatin receptor expression.

RLT represents a valuable therapeutic option for patients with progressive or symptomatic PPGL. Advances in molecular imaging, alphaemitter therapies, and personalized dosimetry are expected to further refine treatment selection and improve outcomes. Larger prospective studies are needed to define optimal sequencing and integration into clinical practice.