Chlorotoxin (CTX) is a small, 36 amino acid neurotoxin isolated from the venom of the Giant Yellow Israeli scorpion Leiurus Quinquestriatus.

Chlorotoxin-tagged cells isolated by flow cytometry and cultured up to two passages exhibit positive labeling for GFAP and vimentin, but not for prolyl 4-hydroxylase (fibroblast), A2B5 (O2A progenitor), or OX-42 (microglia). Expression of a novel chlorotoxin-sensitive Cl(Ca) channel in a morphologically distinct subpopulation of NRAs distinguishes these cells as a new subtype of reactive astrocyte ¹⁾.

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 ²⁾.

Further modification of this radiopeptide with other better imaging isotopes may provide an important tool for determining tumor extent and differentiating regions of viable tumor from necrosis ³⁾.

Superparamagnetic iron oxide nanoparticle (SPIO)-fluorescein isothiocyanate (FITC)-chlorotoxin (SPIOFC) is suitable for the specific and efficient targeting of glioma cells. MRI and optical imaging in conjunction with SPIOFC can differentiate glioma cells from normal brain tissue cells ⁴⁾.

Tumor Paint BLZ-100, a tumor ligand chlorotoxin (CTX) conjugated to indocyanine Green (ICG), has shown potential to be a targeted contrast agent. There are many infrared imaging systems (NIR) in use, but they are not optimized to the low concentration and amount of ICG

BLZ-100 has a very high affinity toward human gliomas. They also describe a small, cost-effective, and sensitive NIR system for visualizing brain tumors tagged using BLZ-100. Butte et al. hope that the use of BLZ-100 along with NIR imaging will be useful to delineate the brain tumors in real-time and assist surgeons in near-complete tumor removal to increase survival and reduce neurological deficits ⁵⁾.