Halogenated pyrimidine analogs such as iododeoxyuridine (IUdR) have been the subject of several recent investigations because of their potential role as clinical radiosensitizers, especially in the treatment of poorly radioresponsive tumors where adjacent normal tissues at risk have low mitotic rates. Preliminary studies indicate that radiosensitization by IUdR can be enhanced substantially with the use of photons of energy ust greater than 33.2 keV, the K-absorption edge of iodine. It has been proposed that the enhancement of IUdR radiosensitization is caused by the release of higher LET radiations in the form of Auger electrons when a photon knocks out the K-shell electron of iodine via photoelectric effect. The clinical potential of this phenomenon will be investigated in this project by examining the effects of photon energy, fractionation and dose rate upon IUdR radiosensitization under aerobic and hypoxic conditions. In order to exploit photon-induced Auger electrons, radiation therapy must be carried out with photons of relatively low energy, such as filtered orthovoltage x-rays or photons from brachytherapy sources. The proposed studies will compare single and fractionated exposures to orthovoltage x-rays with exposures to 4 MeV x-rays and will compare continuous low dose rate irradiations using brachytherapy sources (Am-241) emitting photons with energies just greater than 33.2 keV, the K-absorption edge of iodine with Ir-192 and Ra-226, which emit higher energy photons. Initial studies will be carried out with Chinese hamster cells irradiated in vitro. After determining optimum IUdR incorporation and irradiation techniques, the therapeutic potential of the approach will be examined using a solid rat tumor, (BA1112 sarcoma) irradiated in vivo and assayed for tumor cell survival using an in vitro colony formation assay. Finally, tumor cure experiments, with and without IUdR infusions, will be conducted to investigate the effects of IUdR and photon energy on local tumor control.
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