Synthesis of selenium-75 labeled tertiary diamines: new brain imaging agents

Abstract

Se-75 labeled tertiary diamines, bis[.beta.-(N,N-dimethylamino)ethyl] selenide (1), bis[.beta.-(N,N-diisopropylamino)ethyl] selenide (2), bis(.beta.-piperidinoethyl) selenide (3), and bis(.beta.-morpholinoethyl) selenide (4), were prepared by reducing [75Se]selenious acid with sodium borohydride and reacting the intermediate with the N,N-disubstituted aminoethyl chlorides. The effect of pH on lipid solubility (1-octanol/buffer distribution coefficient) was measured for each labeled compound. Biodistribution studies in rats showed high brain uptake for the tertiary diamines, especially for 3 and 4 (1.53 and 1.49% dose/organ, respectively, at 30 min after i.v. injection). The permanently charged bisquaternary amine, bis[.beta.-(N,N,N-trimethylammonio)ethyl] selenide (5), showed negligible brain uptake (0.06% dose/organ at 30 min).