Analysis of 5-iodo-2′ -deoxyuridine incorporation in murine melanoma for photon activation therapy

Quantitative evaluation of the dose enhancement obtained with analog nucleoside agents such as iododeoxyuridme (IdUrd) requires knowledge of the degree to which the thymidine (Thd) in DNA is replaced by IdUrd. In the present investigation, mice were infused with IdUrd using an intravenous infusion apparatus capable of delivering continuous multi-day infusions without restraining the mice. The absolute incorporation of IdUrd in DNA was measured by 125IdUrd label, both in whole tissue and extracted DNA, showing a good correlation between levels observed in DNA and whole tissue. Replacement in a Harding-Passey murine melanoma tumor carried in BALB/c mice approached 10%. In addition, a Neutron Activation Analysis (NAA) technique was developed which showed in vitro, a sensitivity sufficient to evaluate the ‰ replacement of Thd by IdUrd in small biological samples with a sensitivity greater than 0.1 ppm, at 1 ‰ replacement in mg samples. This method can provide information on iodine substitution in DNA in humans where the. use of a radioactive DNA-seeking substance would be undesirable. Analyses of IdUrd incorporation in cultured cells by NAA and 125I counting showed good agreement.