Steps toward High Specific Activity Labeling of Biomolecules for Therapeutic Application:  Preparation of Precursor [188Re(H2O)3(CO)3]+ and Synthesis of Tailor-Made Bifunctional Ligand Systems

Two kit preparations of the organometallic precursor [188Re(H2O)3(CO)3]+ in aqueous media are presented. Method A uses gaseous carbon monoxide and amine borane (BH3·NH3) as the reducing agent. In method B CO(g) is replaced by K2[H3BCO2] that releases carbon monoxide during hydrolysis. Both procedures afford the desired precursor in yields >85% after 10 min at 60 °C. HPLC and TLC analyses revealed 7 ± 3% of unreacted 188ReO4 - and 95% with [188Re(H2O)3(CO)3]+ under mild reaction conditions (PBS buffer, 60 °C, 60 min) at ligand concentrations between 5 × 10-4 M and 5 × 10-5 M. Thus, specific activities of 22−220 GBq per μmol of ligand could be achieved. Incubation of the corresponding Re-188 complexes in human serum at 37 °C revealed stabilities between 80 ± 4% and 45 ± 10% at 24 h, respectively, and 63 ± 3% and 34 ± 3% at 48 h postincubation in human serum depending on the chelating system. Decomposition product was mainly 188ReO4 -. The routine kit-preparation of the precursor [188Re(H2O)3(CO)3]+ in combination with tailor-made ligand systems enables the organometallic labeling of biomolecules with unprecedented high specific activities.