Anlotinib Enhances 177Lu-DOTA-TOC Antitumor Activity in an SSTR2-Overexpressing PC12 Pheochromocytoma Model Relevant to PPGL: Association with Cytoskeletal Remodeling and Clathrin-Sensitive Internalization

Background

Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine malignancies with limited therapies. Peptide Receptor Radionuclide Therapy (PRRT) with radiolabeled somatostatin analogs is clinically relevant for SSTR-positive disease, since SSTR2 is highly expressed in patients with PPGL. Anlotinib, a multi-tyrosine kinase inhibitor approved in China for several cancers, remains investigational in PPGL. This study evaluated whether anlotinib enhances 177Lu-DOTA-TOC activity in an SSTR2-overexpressing PC12 pheochromocytoma model and examined internalization.