[¹⁸⁸Re(N)(cys∼)(PNP)]^+/0 mixed ligand compounds as models for target specific agents

An efficient procedure for the preparation of [¹⁸⁸Re(N)(PNP)]-based complexes is reported. The radiochemical yield (RCY) of the compounds was optimized considering reaction parameters such as: nature of nitrido nitrogen donors, reaction times and pH.
The chemical identity of ¹⁸⁸Re-agents was determined by high-performance liquid chromatography comparison with the corresponding well characterized cold Re-compounds. The stability of the [¹⁸⁸Re(N)(PNP)] complexes toward transchelation with glutathione and degradation by serum enzymes was assessed. The clearance of selected radiolabeled agents from normal tissues was evaluated in rats.
[¹⁸⁸Re(N)(cys∼)(PNP)]^+/0 asymmetrical compounds were prepared in aqueous solution from perrhenate using a multistep procedure based on the preliminary formation of the labile ¹⁸⁸Re^IIIEDTA species which easily undergo to oxidation/ligand exchange reaction to afford in presence of DTCZ the [¹⁸⁸Re^V≡N]²⁺core. The final compounds were obtained by adding to the [¹⁸⁸Re^V≡N]_int ²⁺ the two bidentate ligands. However, a relative high amount of cys∼ ligand was required to obtain a quantitative RCY. The complexes were stable toward reoxidation to perrhenate and ligand exchange reactions. In vivo studies showed a rapid distribution and elimination of the complexes from the body. No specific uptakes in radiation sensitive tissues/organs were detected.
A positive correlation of the distribution of the complexes estimated with biodistribution studies (% injected dose) andwithmicro-single photon emission computed tomography semiquantification imaging analysis was observed. The low labeling efficiency limits but not excludes the possibility to apply [¹⁸⁸Re(N)(PNP)]-technology to the preparation of target specific radiotherapeutical agents.