3rd-INCC

[188Re(N)(cys~)(PNP)]+/0 mixed ligand compounds as models for the development of target specific agents

22 Sept 2011, 17:30

1h 30m

Paladini (Città del Mare, Terrasini - Palermo - Sicily - Italy)

poster Radiopharmaceuticals Chemistry Poster Section 2

Speaker

Prof. Alessandro Dolmella (University of Padova)

Description

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 established by HPLC comparison with the corresponding well characterized cold Re-compounds. The stability of the [188Re(N)(PNP)]-complexes toward transchelation with GSH 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 188ReIIIEDTA species which easily undergo to oxidation/ligand exchange reaction to afford in presence of DTCZ the [188ReV≡N]2+ core. The final compounds were obtained by adding to the [188ReV≡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 (%ID) and with micro-SPECT semiquantification imaging analysis (SUV) 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.