When certain halogenated pyrimidines such as bromodeoxyuridine (BrdUrd) and iododeoxyuridine (IdUrd) are incorporated into cellular DNA, cells become more sensitive to ionizing radiation and chemotherapy drugs. This observation has led to several clinical studies over the years and recently at the NCI to evaluate whether selective sensitization of tumors could be achieved by IdUrd infusion followed by radiation. An important question arises in these studies regarding the extent to which the drug is incorporated into cells. Work continues to develop techniques to quantify IdUrd incorporation into tumor and normal tissues. The IdUrd monoclonal antibody has proven useful in flow cytometry studies to accurately predict the labeling index (proportion of cells in S phase) and the laboratory is currently involved (with the clinical IdUrd study) in assessing this potentially important clinical parameter. We have obtained biopsied material from at least 10 patients who have received protracted IUdR intravenous infusion. Our findings to date have been that the replacement of thymidine with IUdR has been relatively low from most all patients ranging from 1-10%. However, it is to early to make a statement regarding the extent of replacement with the overall radiotherapy treatment outcome. We will continue to collect and evaluate IUdR replacement data from patients over the next year. Of significance was the observation that one patient who had received a five day infusion of IUdR with a replacement of 10% had a dramatic complete response of a large bulky head and neck lesion. Use of the IUdR antibody and image analysis has enabled us to assess each patient with respect to the heterogeneity of lUdR incorporation. We have automated this process such that it is feasible to determine a labelling index and a measure of heterogeneity from an entire tissue section. In addition to use of the lUdR antibody we are also using the Ki-67 antibody which should complement our studies by giving us an estimate of the growth fraction of the tumor.
