Cellular damage by Auger electrons from ¹²³ I

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ABSTRACT

Auger electrons have the potential for therapy mainly because of their short range and high level of toxicity. Biological effects of these electrons are critically dependent on the cellular and sub-cellular localization of their emitters. In this

study~

1231 was used due to its relatively short half-life (13.2 h) and ideal y-ray energy (Ey=I59 keV). The short half-life is advantageous since it allows significant accumulation of disintegrations at normal physiological conditions without the need to freeze cells as required when long lived

iso~~pes

such as 1251 (Ttn=60.1 days) are used.

The main objective of this study was to synthesize an organic compound that would deliver the radioactive 1231 into cellular DNA and to quantify the resulting damage from micronucleation.

The higher degree of damage obtained in cell samples treated with

4-rt

23I]iodoantipyrine than

with

rt

23IJNal is an indication of Auger electron effect. Also, micronuclei counts showed that

4-[12~iodoantipyrine and [123I]Nal were prepared in a suitable manner and did not interfere with cellular kinetics. RBE values of 1.8 and 1.9 were obtained for CHO-Kl clone# 7 and# 16 cells, respectively, indicating lack of differential response for the two clones. When the current data is collectively analyzed with that of other investigators using the same radiolabeled compounds, a reduction in Auger electron RBE is noticeable with radiosensitivity. This is consistent with the high-LET nature of Auger electrons. The extremely radiosensitive CHO-XRS 1 failed to give a dose-response as most cells underwent apoptosis. The, significant radioprotection of CHO-Kl

cells irradiated, in the presence of a chemical protector MEA, with 4-[ 123I]iodoantipyrine than with

e

23I]Nal showed

that

the mode

by

which Auger electrons cause damage is not the same as that of a-particles. Further studies involving the use of carriers that would specifically deliver radionuclides to nuclear DNA may be useful in understanding the mechanisms underlying the cellular responses to Auger electron exposure.

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