AbstractFor the purposes of evaluation of the therapeutic potential of the radiohalogenated thymidine analogue125IUdR, estimation of the radiation dose to the tumour cells and normal tissues is important. To determine the dose to any tissue from the radionuclide125I is not simple, since the major emissions are very short-range Auger electrons. The cytotoxicity of125I is strongly dependent on the position of the decay relative to the DNA, the principal target for cell sterilization. Estimates of the cytotoxicity of125I based on the traditional MIRD recommended formulation (ICRU Report 32, 1979) may produce gross underestimates if it is incorporated into the DNA via the thymidine precursor125IUdR. In this work, tissue count and autoradiography (ARG) data from studies by Bagshawe et al were used to estimate tissue doses following the administration of125IUdR to LS174/T (a colorectal carcinoma) and CC3 (a choriocarcinoma) tumour-bearing animals, after a hydroxyurea block of the normal tissue turnover. The tumour cell toxicity is estimated from ARG data on the degree of125I incorporation into the cell nucleus. Major drawbacks with125I for this type of therapy are the long 60-day half-life, leading to radiological and waste disposal problems and the extreme short range of the radiotoxic effects. Possible alternative radiohalogens,123I,77Br,131I and211At, are suggested in place of125I in the thymidine analog iododeoxyuridine. Dose calculations are performed and cytotoxicities estimated on the assumption that their biological retention characteristics are the same as for125IUdR.