High-yield synthesis of the terminal 188Re≡N multiple bond from generator-produced [ 188ReO 4] −

Abstract

A novel procedure for the high-yield preparation of Re-188 radiopharmaceuticals containing a terminal Re≡N multiple bond is described. This method involves the reaction of [ 188Re][ReO 4] − with N-methyl S-methyl dithiocarbazate (DTCZ), as donor of nitrido nitrogen atoms, sodium oxalate and SnCl 2 to afford a mixture of two intermediate compounds. When this mixture is reacted with the sodium salt of a dithiocarbamate ligand (L) of the type Na[R 2N-C(=S)S] (R = CH 3, CH 3CH 2, CH 3CH 2CH 2), the formation of the bis-substituted, neutral complexes [ 188Re][Re(N)(L) 2] is easily obtained in high yield (> 95%). The complexes [ 188Re][Re(N)(L) 2] were characterized by chromatographic methods, and by comparison with the corresponding complexes prepared at macroscopic level starting from a non-radioactive rhenium precursor. Biodistribution studies were carried out in rats. Results showed that the complexes [ 188Re][Re(N)(L) 2] exhibited the same biological behavior of the analogous Tc-99m complexes reported previously. The easy application of the new synthetic procedure indicates that it could be conveniently employed for preparing a large class of new Re-188 complexes having potential utilization in nuclear medicine as therapeutic agents.