An alternative approach to the preparation of Re-188 radiopharmaceuticals from generator produced [(ReO4)-Re-188](-): Efficient synthesis of Re-188(V)-meso-2,3-dimercaptosuccinic acid

A new efficient approach for the preparation of Re-188 radiopharmaceuticals starting from [(ReO4)-Re-188](-), produced at a carrier free level through the W-188/Re-188 generator system, is described. The reaction procedure wa s based on the combined action of different reagents and has been applied i n detail to the preparation of the therapeutic agent Re-188(V)-DMSA (H(2)DM SA [meso-2,3-dimercaptosuccinic acid]). The most efficient combination requ ired the use of SnCl2, oxalate ions, and gamma-cyclodextrin. These were rea cted with [(ReO4)-Re-188](-) and H(2)DMSA to afford the final radiopharmace utical in high radiochemical purity, at room temperature, and in weakly aci dic solution. The role played by the various reagents in the reaction was i nvestigated. It was found that SnCl2 behaved as the actual reducing agent, whereas oxalate and gamma-cyclodextrin greatly enhanced the ease of reducti on of [(ReO4)-Re-188](-) through the action of two hypothetical mechanisms. In the first step of the reaction, oxalate ions gave rise to the formation of Re(VII) complexes with the concomitant expansion of the coordination sp here of the metal. This process strongly favored the electron transfer betw een Sn2+ and Re+7 centers, giving rise to intermediate reduced rhenium comp lexes. These species were further stabilized by the formation of transient host guest aggregates with gamma-cyclodextrin and finally converted into Re -188(V)-DMSA through simple replacement of the coordinated ligands by H(2)D MSA. NUCL MED BIOL 27;3:309-314, 2000. (C) 2000 Elsevier Science Inc. All r ights reserved.