Targeted
therapies for
cancer is a rapidly advancing field, but the identification of
tumor-specific
ligands has proven difficult.
Chlorotoxin (CTX) is a small, 36
amino acid neurotoxin isolated from the
venom of the Giant Yellow Israeli scorpion Leiurus Quinquestriatus. Interestingly, the
peptide has been found to preferentially bind to a variety of human
malignancies, but shows little or no binding to normal human tissues. A synthetic version of this
peptide (TM-601) has been manufactured and covalently linked to
iodine 131 (131I-TM-601) as a means of targeting radiation to
tumor cells. Preclinical studies and Phase I clinical trials have been completed in patients with recurrent
glioma, a type of malignant
brain tumor. These studies demonstrated that intracavitary dosing of
131I-TM-601 appears safe, minimally toxic, and binds
malignant glioma with high affinity and for long durations. A Phase II trial of this agent using higher doses of radioactivity and repeated local administrations is underway. In addition, enrolment has begun in a Phase I trial evaluating whether systemically delivered
131I-TM-601 can be used to image metastatic solid
tumors and primary
gliomas. Due to its small size, selective
tumor binding properties, minimal toxicity and relative ease of manipulation, CTX represents a potentially important targeting agent for many
cancers.