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.

journal_name

Gynecol Obstet Invest

authors

Rotmensch J,Schwartz JL,Atcher RW,Harper PV,DeSombre E

doi

10.1159/000293025

subject

Has Abstract

pub_date

1991-01-01 00:00:00

pages

180-4

issue

3

eissn

0378-7346

issn

1423-002X

journal_volume

32

pub_type

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