Radiation dosimetry of 131I-chlorotoxin for targeted radiotherapy in glioma-bearing mice

Chlorotoxin, or TM-601, is a peptide derived from the venom of the scorpionLeiurus Quinquestriatus that specifically binds to malignant brain tumors, but not to normal tissues. Targeted radiotherapy using ¹³¹I-Chlorotoxin is promising for post-surgery treatment of brain tumors. This study reports dosimetry results of ¹³¹I-Chlorotoxin in athymic nude mice with intracranially implanted human glioma xenografts and projected radiation doses in patients receiving 370 MBq of ¹³¹I-Chlorotoxin. ¹²⁵I/¹³¹I-Chlorotoxin were injected into the right brain where D54 MG xenografts were implanted. Mice were sacrificed 24–96 h later. The blood, normal organs, and tumors were weighed and counted to determine ¹³¹I-Chlorotoxin concentration. The radiation dose from ¹³¹I was calculated based on non-penetrating radiation in the mouse model. Assuming similar tissue uptake in mice and patients, radiation doses for patients were extrapolated. Distributions of ¹²⁵I/¹³¹I-Chlorotoxin were only significant in tumor, stomach, kidneys, and brain (injection site), reflecting non-specific uptake of Chlorotoxin in normal tissues. Mean radiation dose (cGy/37kBq) was 58.2 for tumor, 17.9 for brains, 1.8 for marrow, 27.1 for stomach, 16.0 for kidneys in mice. For intracranial injection of 370MBq ¹³¹I-Chlorotoxin in patients, extrapolated patient dose (cGy) was 70 for brains, 6 for marrow, 35 for stomach, 60 to kidneys, 227 to tumor, suggesting that 3.7GBq of ¹³¹I-Chlorotoxin can be safely administrated to patients. These promising results demonstrated potential in improving patient survival using this novel targeting agent.