Preparation and biological evaluation of technetium-99m-L,L-propylenedicysteine

In this study we have investigated the influence of replacement of the ethy lene moiety in Tc-99m-L,L-ethylenedicysteine (Tc-99m-L,L-EC) by a propylene moiety on the physical and biological properties. S,S'-dibenzyl-N,N'-1,3-propylenediylbis-L-cysteine was synthesised by react ion of S-benzyl-1-cysteine with 1,3-dichloropropane, The thiol groups were deprotected with sodium in liquid ammonia. The resulting L,L-propylenedicys teine (L,L-PC) was directly labelled with Tc-99m at pH 12. Whereas labellin g of L,L-EC results in a single radiochemical species, labelling of L,L-PC yields two Tc-99m-complexes in a 3/1 ratio, probably two isomers with the c entral propylene carbon atom syn or anti to the oxotechnetium core. These i somers are stable and do not interconvert at neutral pH. In mice, both isom ers of Tc-99m-L,L-PC showed a slower urinary excretion and a higher hepatob iliary uptake than Tc-99m-L,L-EC. Furthermore, Tc-99m-L,L-PC showed some re nal retention. In a baboon, both conformers of Tc-99m-L,L-PC were excreted rapidly in the urine without visualisation of liver or intestines, but thei r plasma clearance was only 33.6% of hippuran clearance for isomer A and 25 .6% for isomer B, as compared to 75% in the case of Tc-99m-L,L-EC. The results indicate that, besides the oxotechnetium-glycine sequence, also the length and orientation of the alkylene bridge between the two amines a re important for the interaction of this type of compounds with the renal t ubular transport proteins.