Radiation Dosimetry, Pharmacokinetics, and Safety of Ultratrace™ Iobenguane I-131 in Patients with Malignant Pheochromocytoma/Paraganglioma or Metastatic Carcinoid

This is a first of many phase 1 study of Ultratrace (TM) Iobenguane I-131 (Ultratrace (131)I-MIBG; Molecular Insight Pharmaceuticals, Inc., Cambridge, MA). High-specific-activity Ultratrace (131)I-MIBG may provide improved efficacy and tolerability over carrier-added (131)I-MIBG. We investigated the pharmacokinetics (PK), radiation dosimetry, and clinical safety in 11 patients with confirmed pheochromocytoma/paraganglioma (Pheo) or carcinoid tumors. A single 5.0-mCi (185 MBq) injection of Ultratrace (131)I-MIBG, supplemented with 185 mu g of unlabeled MIBG to simulate the amount of MIBG anticipated in a therapeutic dose, was administered. Over 120 hours postdose, blood and urine were collected for PK, and sequential whole-body planar imaging was performed. Patients were followed for adverse events for 2 weeks. Ultratrace (131)I-MIBG is rapidly cleared from the blood and excreted in urine (80.3% +/- 2.8% of dose at 120 hours). For a therapeutic administration of 500 mCi (18.5 GBq), our estimate of the projected dose is 1.4 Gy for marrow and 10.4 Gy for kidneys. Safety results showed 12 mild adverse events, all considered unrelated to study drug, in 8 of 11 patients. These findings support the further development of Ultratrace (131)I-MIBG for the treatment of neuroendocrine tumors, such as metastatic Pheo and carcinoid.