Pharmaceuticals
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
By Rui Tian, Fan Qiu, Bo Luo and 4 others.
Abstract
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.
Methods
PC12-SSTR2 cell and vector control were generated. PC12-SSTR2 cells were treated with anlotinib, 177Lu-DOTA-TOC, or their combination to assess viability, clonogenic growth, apoptosis, DNA damage, cytoskeletal morphology, and internalization. Endocytosis was probed with chlorpromazine, filipin, EIPA, and colchicine. BALB/c nude mice bearing PC12-SSTR2 xenografts received control, monotherapy, or combination with PRRT on Day 1, 4, or 7 of anlotinib.