title: [131I]IAZA as a molecular radiotherapeutic (MRT) drug: wash-out with cold IAZA accelerates clearance in a murine tumor model.
abstract: Based on animal model studies, [131I]IAZA may be useful as an adjunct radiotherapeutic (MRT) drug for the treatment of tumor hypoxia. However, radioactivity in the blood of patients and healthy volunteers dosed with [123I]IAZA has a protracted terminal elimination phase in which clearance is influenced by free [123I]IAZA and possibly by unidentified metabolites. The current work reports that about 40% of the radioactivity in human serum is associated with the serum protein fraction, and that the free:bound ratio is constant at about 60:40 for at least the first 135 min after injection, as determined by radio-HPLC analyses. In order to modulate the clearance of bound and free radioactive IAZA, nonradioactive (cold) IAZA was administered i.v. 1 h following injection of high specific activity [125I][IAZA in the Balb/C EMT-6 murine tumor model. This 'wash out' procedure reduced the concentrations of radioactivity by at least 40% in all tissues, with greatest effect in kidney and liver, and least in tumor. As a result, the tumor:blood ratio increased from 5.8 to 8.5 at 4 h post-injection. This effect would be advantageous for the use of [131I]IAZA as an MRT drug. Optimization of intervals between radioactive and wash out dose, and confirmation of the self-irradiation dose to all tissues, remain to be undertaken before [131I]IAZA can be tested as a low-dose-rate MRT supplement to external beam x-ray radiotherapy.
authors.affiliation: Division of Oncological Imaging, 1807 Cross Cancer Institute, Edmonton, T6G 1Z2, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: Mercer
authors.forename: Alexander J B
authors.initials: AJ
authors.lastname: McEwan
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Wiebe
mesh_terms: D000818:Animals; D003080:Cold Temperature; D064368:Healthy Volunteers; D006801:Humans; D007457:Iodine Radioisotopes / Q000097:blood / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy*; D009593:Nitroimidazoles / Q000097:blood / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D007457:Iodine Radioisotopes; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; C070588:iodoazomycin arabinoside