188Re(V)-DMSA: in-vitro and in-vivo studies on the individual stereo isomers

The pentavalent rhenium-188 meso-dimercapto-succinic acid complex 1 8 8 Re(V)-DMSA is a beta-emitting analogue of Tc99 m (V)-DMSA, an established tracer that is taken up in a variety of histological different tumors and especially in bone metastases arising from breast and prostate carcinomas. The similar general biodistribution and tumor avidity of 1 8 8 Re-and 9 9 m Tc(V)-DMSA therefore suggests the use of the rhenium analog as an agent for therapeutic applications. No-carrier-added 1 8 8 Re(V)-DMSA is composed of a mixture of three stereoisomers arising from different orientations of the 4 carboxylate groups of the complex. For therapeutic applications it must be known whether there is a difference in the in-vivo biodistribution and kinetics of the individual stereo isomers. The aim of this study was therefore a) to characterize the chemical stability of each of the 3 stereoisomers with respect to time, temperature and pH and b) to evaluate if there are differences in the in-vivo organ distribution of the pure isomers compared to the isomeric mixture. The in-vitro results revealed for all three individual isomers of 1 8 8 Re(V)-DMSA a rather slow (with respect to half-life of Re-188) temperature and pH dependent rate of interconversion which would justify the application of pure isomers. The data obtained from urine samples of rats showed a faster interconversion rate and reached a stable isomer distribution after about six to ten hours, depending on which isomer was injected. However there was no evidence for isomer specific excretion rates. The organ biodistribution patterns of all three isomers were very similar at all times studied (10 min up to 24 hours p.i). The tumor uptake in a rat mammary carcinoma model at 1 hour p.i. did also not show any significant differences. In conclusion the preparation and administration of pure stereoisomers of 1 8 8 Re-DMSA is possible, however, in-vivo no significant differences in organ distribution and kinetics were observed which would favour the use of purified stereo isomers over the isomeric mixture of 1 8 8 Re(V)-DMSA.