Radioprotection Against Biological Effects of Internal Radionuclides In Vivo by S-(2-Aminoethyl)isothiouronium Bromide Hydrobromide (AET)

Radionuclides employed in diagnostic and therapeutic nuclear medicine impart radiation energy to tissue over an extended period of time, which depends on the physical half-life and the biological properties of the radiochemical employed. It is therefore important to examine the capacity of chemical radioprotectors to mitigate damage caused by chronic irradiation by incorporated radionuclides. Methods: Spermatogenesis in mouse testis is used as the experimental model, and spermatogonial cell survival as measured by testicular spermhead count is the biological end point. The capacity of S-(2-aminoethyl)isothiouronium bromide hydrobromide (AET) to mitigate radiation damage caused by chronic irradiation by the radiochemicals (125)IUdR, H(125)IPDM and Po-210-citrate, is investigated. Results: The radioprotection provided by AET is substantial and similar for both of the radioiodinated compounds with dose modification factors (DMF) of 4.0 +/- 1.2 for (125)IUdR and 3.4 +/- 0.4 for H(125)IPDM. In contrast, the damage caused by Po-210 alpha particles is protected against to a lesser degree (DMF = 2.4 +/- 0.5). Conclusion: The present radioprotection data for AET, in conjunction with our earlier findings for the chemical protectors cysteamine and vitamin C in the same experimental model, suggest that such compounds may be clinically useful as mitigating agents against biological damage caused by incorporated radionuclides. The observed DMFs for AET also support our earlier premise that the mechanism by which DNA-incorporated Auger emitters impart biological damage is primarily radical mediated, and hence indirect in nature.