Radiation enhancement with 127I-deoxyuridine

A technique for radiation enhancement of photon radiotherapy is outlined. High LET radiations in the form of Auger electron distributions are generated by photoactivation of stable iodine incorporated as iodinated deoxyuridine (IdUrd). Of the several halogenated deoxyribonucleosides evaluated, IdUrd was found to be the only thymidine analog providing effective photoactivation. This mechanism is combined with radiation sensitization to produce an overall radiation enhancement. Calculations show that 5% replacement of Tyd in tumor DNA should multiply the biological effectiveness of low energy photons by a factor of approx. 2. Higher replacements would provide higher gains. Enhancement results from chemical sensitization by IdUrd, where it is known that effects of irradiation are multiplied by factors of from approx. 1.5 to 3 as replacement varies from 10 to 50%. Additional enhancement results from the stimulation of Auger cascades in DNA. Five percent replacement has been obtained in human tumor in vivo. Twice that has been obtained in murine tumors. Our data indicates that damage from photoactivation as well as chemical sensitization does not repair. Thus, it is anticipated that use of low dose rates associated with permanent implants of Sm-145 sources (38-45 KeV x-rays; T1/2 = 340 d) will yield an additional increase in therapeutic efficacy by a factor of from 3 to 8, compared to that obtained with acute dose rates