131I-TM601 (131I-Chlorotoxin) is a synthetic radiolabeled peptide with anti-angiogenic activity in neovascular diseases under development for the treatment of primary tumors and metastases in the periphery and in the central nervous system. In February 2002 the drug was granted FDA orphan drug status in glioma and in August 2003 the molecule obtained Fast Track designation.

131I-TM601 is based on the peptide TM601 which is used as a vector to bring a cytotoxic element to the tumor. In the case of 131I-TM601, a radionuclide is used as a payload. TM601, is a synthetic version of Chlorotoxin, a 36 amino acid small peptide originally isolated from the giant Israeli scorpion. The peptide has a highly specific tumor cell binding, uptake and internalization based on the affinity for Annexin A2, a receptor expressed on a wide range of tumor cells but not on normal, healthy cells. The peptide alone has in vivo anti-angiogenic activity, due to its ability to bind to and inhibit matrix metalloproteinase 2 (MMP-2), an endopeptidase involved in angiogenesis.

A Phase I safety trial concluded that it is possible to use 131I-TM601 at single doses of up to 100 mCi. A trial was performed on patients with glioma and the drug was injected intracavitary. Tests with small iv doses demonstrated a biodistribution in tumors including in glioma and melanoma patients. The drug easily crosses the BBB and for therapy of glioma patients, iv treatment can replace intracavitary injection. Six Phase I and II clinical studies have been initiated in glioma patients and melanoma patients, and some of them completed between 2002 and 2009. Unfortunately, since 2009, no new study was started with this molecule.

Target/Mechanism: Annexin

Carrier/Ligand: Chlorotoxin

Radiation Type: beta electrons (β)

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