title: Optimal photon energies for IUdR K-edge radiosensitization with filtered x-ray and radioisotope sources.
abstract: The purpose of this work is to determine the most physically effective radiation energy for K-edge absorption of x- or gamma-rays by iododeoxyuridine (IUdR) on Chinese hamster ovary (CHO) cells. Brachytherapy sources (Sm-145, I-125, Yb-169 and Am-241) and x-ray beams (30 kVp, 100 kVp and 100 kVp with gold, gadolinium, lead or tungsten filtration) were investigated for their preferential absorption qualities by IUdR sensitized DNA. The 30 kVp, 100 kVp and 100 kVp with tungsten filtration were then used to irradiate CHO cells, with or without IUdR incorporation (i.e. 10(-5) M of IUdR for 3 days). Radiation absorption calculations were performed to determine the increase in energy absorption in DNA with and without IUdR incorporated. In order to measure the in vitro biological effects of K-edge absorption, cell survival experiments were performed. The radiation physics calculations yielded an iodine dose enhancement ratio (DER) of 1.4+/-0.15. 1.8+/-0.15 and 2.7+/-0.15 for the 30 kVp, 100 kVp and tungsten filtered 100 kVp respectively, for 18% IUdR replacement of thymidine in DNA. The corresponding cell sensitization enhancement ratios (SER), determined from the cell survival assay, were determined to be 1.24+/-0.2, 1.8+/-0.2 and 2.3+/-0.3 for the 30 kVp, 100 kVp and tungsten filtered 100 kVp respectively, for cells with 18+/-2% IUdR incorporation. These SER values are in reasonable agreement with the DER values of 1.4, 1.8 and 2.7. From these radiation calculations and radiobiology experiments we confirm that using x-radiation energies above the K-edge of iodine (33.2 keV) can have a significant effect on cell survival. This effect is due mainly to the increase in the local dose to the DNA for IUdR-sensitized cells compared with the normal DNA which lacks the iodine contrast agent. Our results support the clinical application of IUdR and low-energy brachytherapy, perhaps using new technologies such as the x-ray needle or new isotopes such as Yb-169.
authors.affiliation: Department of Medical Biophysics, University of Western Ontario, London, Canada.
authors.forename: S J
authors.initials: SJ
authors.lastname: Karnas
authors.forename: E
authors.initials: E
authors.lastname: Yu
authors.forename: R C
authors.initials: RC
authors.lastname: McGarry
authors.forename: J J
authors.initials: JJ
authors.lastname: Battista
mesh_terms: D000576:Americium; D000818:Animals; D001918:Brachytherapy / Q000379:methods; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D007065:Idoxuridine / Q000493:pharmacokinetics / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D017785:Photons; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D011868:Radioisotopes; D012493:Samarium; D014965:X-Rays; D015018:Ytterbium
chemical_list: D007457:Iodine Radioisotopes; D011838:Radiation-Sensitizing Agents; D011868:Radioisotopes; D012493:Samarium; D004247:DNA; D007065:Idoxuridine; D015018:Ytterbium; D000576:Americium