title: Increased nuclear damage by high linear energy transfer radioisotopes applicable for radiodirected therapy against radiologic malignancies.
abstract: High linear energy transfer radioisotopes carried by appropriate agents have been proposed for receptor-directed radiotherapy. Two such classes of isotopes are Auger electron and alpha-emitting nuclides. To determine the relative cytotoxicity and nuclear damage to cells produced by these two classes of nuclides, we compared bromine-80m (80mBr), an Auger-electron-emitting radionuclide with a 4.4-hour half-life, with bismuth-212 (212Bi), an alpha-emitter with a 1-hour half-life. Because of the short path length of the Auger electrons, 80mBr was radiotoxic only when incorporated into DNA, such as in the form of [80mBr]bromodeoxyuridine ([80mBr]BrUdR). Both agents induced linear increases in chromosome aberration frequency, however, [80mBr]BrUdR caused multiple aberrations including the shattering of parts of the chromosomes. While, in contrast, a 2-hour exposure of cells to 212Bi, chelated to DTPA, a form which does not enter the cell, induced much less extensive chromosome damage. Exposure to equivalent activities of Auger electrons or alpha-particles results in 5 times more damage in Auger-electron-exposed cells. However, estimates of dose suggest they are equally toxic. Unlike Auger electrons, alpha-particles did not need to be in as close proximity to the DNA to have clastogenic and radiotoxic effects.
authors.affiliation: Department of Obstetrics and Gynecology and Gynecologic Oncology, University of Chicago, Ill.
authors.forename: J
authors.initials: J
authors.lastname: Rotmensch
authors.forename: J L
authors.initials: JL
authors.lastname: Schwartz
authors.forename: R W
authors.initials: RW
authors.lastname: Atcher
authors.forename: P V
authors.initials: PV
authors.lastname: Harper
authors.forename: E
authors.initials: E
authors.lastname: DeSombre
mesh_terms: D000512:Alpha Particles; D000818:Animals; D001729:Bismuth; D001967:Bromine Radioisotopes; D016466:CHO Cells / Q000528:radiation effects; D002470:Cell Survival; D002875:Chromosomes / Q000528:radiation effects*; D006224:Cricetinae; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004583:Electrons; D004735:Energy Transfer; D011868:Radioisotopes
chemical_list: D001967:Bromine Radioisotopes; D011868:Radioisotopes; D004247:DNA; D001729:Bismuth