[³⁵S]cysteamine: Facile synthesis, in vivo biokinetics, and subcellular distribution

Whereas chemical radioprotection against external beams of ionizing radiation is well studied in radiobiology, the aspects relating to tissue incorporated radionuclides have received little attention. The increased use of radionuclides in diagnostic and therapeutic nuclear medicine, as well as the presence of both manmade and natural radioactivity in the environment, indeed call for such investigations. Our ongoing work on a variety of radioprotectors has revealed that cysteamine (MEA), S-2-aminoethylisothio uroniumbromide hydrobromide (AET), and others (e.g. ascorbic acid), protect spermatogonial cells in mouse testis from the effects of chronic irradiation with intratesticularly localized radionuclides. In these experiments, dose modification factors ranging from 2 to 4 and 10 to 14 were obtained using spermhead survival and induction of spermhead abnormalities, respectively, as the biological end points. Similar experiments were carried out by changing the mode of administration of cysteamine to oral intubation. In these studies a dose modification factor of ~3 was observed in the spermhead survival assay. In an effort to understand the protection offered by MEA, the present work describes a one-pot synthesis of high specific activity [³⁵S]cysteamine from elemental [³⁵S]sulphur and its use in determining the biokinetics and biodistribution of MEA following intratesticular (i.t.) or oral administration in mice.