title: Radiation dosimetry of 131I-chlorotoxin for targeted radiotherapy in glioma-bearing mice.
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.
authors.affiliation: Department of Radiation Oncology, Birmingham, AL 35249, USA. ssh-en@uabmc.edu
authors.forename: Sui
authors.initials: S
authors.lastname: Shen
authors.forename: M B
authors.initials: MB
authors.lastname: Khazaeli
authors.forename: G Yancey
authors.initials: GY
authors.lastname: Gillespie
authors.forename: Vernon L
authors.initials: VL
authors.lastname: Alvarez
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D005910:Glioma / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011874:Radiometry; D011878:Radiotherapy; D012604:Scorpion Venoms / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D007457:Iodine Radioisotopes; D012604:Scorpion Venoms; C091539:Chlorotoxin