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.