e14507 Background: Pre-clinical studies demonstrate TM601 binding to glioblastoma, melanoma, and other tumor types in vitro and in vivo (human xenograft tumors in mice). Here we report imaging and safety data from a Phase I clinical trial in patients with recurrent metastatic somatic and/or cerebral solid tumors that received IV (131)I-TM601. METHODS: Patients received an IV imaging test dose of 10 mCi/0.2mg (131)I-TM601. Subjects not showing tumor localization, received a second imaging test dose of 20 mC/0.4mg (131)I-TM601. Subjects without localization at either dose were dropped from study; patients showing tumor localization without toxicity then received a 30 mCi/0.6mg (131)I-TM601 IV injection. The primary objectives were to: 1) determine whole body localization and dosimetry, 2) estimate the maximum tolerated dose based on normal tissue dosimetry and 3) determine the acute toxicity of IV (131)I-TM601. RESULTS: A total of 44 evaluable patients received IV doses of (131)I-TM601 without dose-limiting toxicity. 31/44 (70%) showed tumor specific uptake on follow-up gamma camera or SPECT imaging. Tumor-specific uptake was observed in patients with malignant glioma (7/8), metastatic melanoma (7/7), non-small cell lung cancer (3/4), colon cancer (6/7), pancreatic cancer (2/3), prostate cancer (2/2), breast cancer (1/4) and in one evaluable patient each with transitional cell carcinoma, pleomorphic xanthoastrocytoma and metastatic paraganglioma. Notably, all patients with metastatic cerebral disease showed tumor-specific uptake of systemically injected (131)I-TM601. No uptake was seen in CNS lymphoma (n=1), ovarian (n=2), small cell lung (n=2), or medulllary thyroid cancers (n=1). CONCLUSIONS: Tumor-specific uptake of IV (131)I-TM601 in primary and metastatic (including brain) solid tumors suggests that further dose escalation is warranted. Notably, IV injected (131)I-TM601 crossed the blood brain barrier. Based on normal tissue dosimetry from this study, future clinical trials will evaluate safety and therapeutic efficacy in patients with recurrent glioma and metastatic melanoma at doses up to 100 mCi (131)I-TM601 (maximum single dose). [Table: see text].