[131I]IAZA as a Molecular Radiotherapeutic (MRT) Drug: Wash-Out with Cold IAZA Accelerates Clearance in a Murine Tumor Model

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.