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

J Neurooncol. 2005 Jan;71(2):113-9. doi: 10.1007/s11060-004-0890-4.

Abstract

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/37 kBq) 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 370 MBq 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 3.7 GBq of 131I-Chlorotoxin can be safely administrated to patients. These promising results demonstrated potential in improving patient survival using this novel targeting agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / radiotherapy*
  • Glioma / metabolism
  • Glioma / radiotherapy*
  • Humans
  • Iodine Radioisotopes / pharmacokinetics
  • Iodine Radioisotopes / therapeutic use*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Radiometry
  • Radiotherapy
  • Scorpion Venoms / pharmacokinetics
  • Scorpion Venoms / therapeutic use*
  • Tissue Distribution
  • Transplantation, Heterologous

Substances

  • Iodine Radioisotopes
  • Scorpion Venoms
  • Chlorotoxin