An alternative approach to the preparation of 188Re radiopharmaceuticals from generator produced [188ReO4]-:: Efficient synthesis of 188Re(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 was based on the combined action of different reagents and has been applied in detail to the preparation of the therapeutic agent Re-188(V)-DMSA (H(2)DMSA [meso-2,3-dimercaptosuccinic acid]). The most efficient combination required the use of SnCl2, oxalate ions, and gamma-cyclodextrin. These were reacted with [(ReO4)-Re-188](-) and H(2)DMSA to afford the final radiopharmaceutical in high radiochemical purity, at room temperature, and in weakly acidic solution. The role played by the various reagents in the reaction was investigated. It was found that SnCl2 behaved as the actual reducing agent, whereas oxalate and gamma-cyclodextrin greatly enhanced the ease of reduction 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 sphere of the metal. This process strongly favored the electron transfer between Sn2+ and Re+7 centers, giving rise to intermediate reduced rhenium complexes. 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)DMSA. NUCL MED BIOL 27;3:309-314, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.