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

Division of Radiation Research, Department of Radiology, University of Medicine and Dentistry of New Jersey, Newark, New Jersey

Correspondence: For correspondence or reprints contact: Dandamudi V. Rao, PhD, Division of Radiation Research, MSB F-451, University of Medicine and Dentistry of New Jersey, 185 South Orange Ave., Newark, NJ 07103.

ABSTRACT

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 ¹²⁵IUdR, H¹²⁵IPDM and ²¹⁰Po-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 ¹²⁵IUdR and 3.4 ± 0.4 for H ¹²⁵IPDM. In contrast, the damage caused by ²¹⁰Po 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 DMA-incorporated Auger emitters impart biological damage is primarily radical mediated, and hence indirect in nature.

Key Words: radioprotection • AET • internal radionuclides • Auger electrons • spermatogenesis

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				G. Grafstrom, B.-A. Jonsson, A. M. El Hassan, J. Tennvall, and S.-E. Strand Rat testis as a radiobiological in vivo model for radionuclides Radiat Prot Dosimetry, April 1, 2006; 118(1): 32 - 42. [Abstract] [Full Text] [PDF]