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

Abstract

In this study we have investigated the influence of replacement of the ethylene moiety in 99mTc-L,L-ethylenedicysteine (99mTc-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 reaction of S-benzyl-L-cysteine with 1,3-dichloropropane. The thiol groups were deprotected with sodium in liquid ammonia. The resulting L,L-propylenedicysteine (L,L-PC) was directly labelled with 99mTc at pH 12. Whereas labelling of L,L-ED results in a single radiochemical species, labelling of L,L-PC yields two 99mTc-complexes in a 3/1 ratio, probably two isomers with the central propylene carbon atom syn or anti to the oxotechnetium core. These isomers are stable and do not interconvert at neutral pH. In mice, both isomers of 99mTc-L,L-PC showed a slower urinary excretion and a higher hepatobiliary uptake than 99mTc-L,L-EC. Furthermore, 99Tc-L,L-PC showed some renal retention. In a baboon, both conformers of 99mTc-L,L-PC were excreted rapidly in the urine without visualisation of liver or intestines, but their 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 99mTc-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 are important for the interaction of this type of compounds with the renal tubular transport proteins. Copyright © 1999 John Wiley & Sons, Ltd.