Radiation dosimetry of I-131- TM-601 peptide for synergistic targeted radiotherapy for malignant glioma in mice

Abstract

Purpose/Objective: The benefit of postoperative radiotherapy for glioma patients has been well established where an improvement in median survival was found with increased radiation dose. Dose from external beam radiotherapy is limited by normal brain toxicity. Brachytherapy can deliver higher radiation doses contained within short distance beyond resected tumor cavity wall. However, implants with traditional solid sources require a second invasive procedure, and often fail to tailor the dose distribution to individual target volume. One novel approach is to use radiolabeled target molecules to penetrate and deliver localized radiation to the tumor cells. TM-601 (also called chlorotoxin, TransMolecular, Inc. Birmingham, AL) is a peptide derived from the venom of the scorpion Leiurus Quinquestriatus that specifically binds to malignant brain tumors, but not to normal brain tissue. I-131-TM-601 provides an opportunity for synergy between radiotherapy and biotherapy. Phase I/II human clinical trials are on going, with 10 mCi of I-131-TM-601 directly infused into the resected tumor cavity. This study reports dosimetry results of I-131-TM-601 in athymic nude mice with intracranially implanted human glioma xenografts and projected doses in patients receiving I-131-TM-601.