[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 freebound ratio is constant at about 6040 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 tumorblood 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.