Radiation enhancement with iodinated deoxyuridine.
A technique, Photon Activation Therapy (PAT), is described in which high Linear Energy Transfer (LET) radiations in the form of Auger electron distributions are generated by a photon beam through photoactivation of stable iodine incorporated as an analog of thymidine (Tyd) in DNA. Of the several halogenated deoxyribonucleosides evaluated, iodinated deoxyuridine (IdUrd) was found to be the only viable choice as a Tyd analog for PAT. Calculations show that 5% replacement of Tyd in tumor DNA multiplies the biologic effectiveness of a given photon radiotherapy dose by a factor of approximately 3. If further therapeutic advantages accorded to high LET radiations are taken into account, as well as repair and regeneration of normal tissues during protracted irradiations, an advantage of approximately 6 is realized. Five percent replacement of Tyd has already been reported for human tumor in vivo. Higher replacements of Tyd with IdUrd would provide proportionately greater advantages. The expectation is that previous clinical results with BrdUrd and high-energy X-rays can be significantly improved upon through the use of IdUrd and suitable lower energy activating photons (35-50 keV). In particular, it is suggested that protracted irradiations with implanted sources such as 145Sm or 145Pm may provide unique advantages at selected sites such as brain or head and neck tumors.
D000818:Animals; D004583:Electrons; D004735:Energy Transfer; D006801:Humans; D007065:Idoxuridine / Q000627:therapeutic use*; D051379:Mice; D009369:Neoplasms / Q000532:radiotherapy*; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011882:Radiotherapy, High-Energy / Q000379:methods*
D011838:Radiation-Sensitizing Agents; D007065:Idoxuridine