Phase 1 211At‑MABG targeted alpha radiotherapy (NET/norepinephrine transporter–avid) in advanced NETs

University of Pennsylvania is running a first-in-human Phase 1, open-label, single-group dose-escalation (standard 3+3) study with an RP2D expansion cohort to evaluate fractionated intravenous 211At‑MABG (meta‑astatobenzylguanidine). Mechanistically, 211At is a short‑lived alpha‑particle–emitting radionuclide, and MABG is an MIBG-analog small molecule taken up by norepinephrine transporter–expressing, MIBG‑avid tumors—aiming to deliver high‑LET alpha radiation directly to tumor sites while limiting non-target exposure. Eligible patients are adults with advanced pheochromocytoma/paraganglioma (PPGL) or other MIBG‑avid neuroendocrine cancers (including medullary thyroid cancer, bronchial carcinoid, and gastroenteropancreatic NETs) who need systemic therapy and are refractory to, ineligible for, or lack effective approved options. The key angle is translating targeted alpha therapy into the long-used “MIBG” biology space (historically dominated by beta-emitter 131I‑MIBG in select settings) with a potentially more potent, shorter-range alpha emitter. For metastatic PPGL and other advanced NETs today, care commonly includes somatostatin analogs when appropriate, targeted agents (e.g., TKIs such as sunitinib in PPGL, everolimus in some NETs), PRRT for somatostatin receptor–positive disease, and chemotherapy in select phenotypes—leaving an unmet niche for MIBG‑avid tumors after standard options.