Determination of dissociation kinetics of 188Re(I)-pharmaceuticals by free-ion selective radiotracer extraction

Due to physical decay properties commonly associated with therapeutic radionuclides, 188Re (t1/2 = 16.98 h, Emax = 2.12 MeV) is of high interest for endovascular brachytherapy and endoradiotherapy in general. Rhenium precursors in the low oxidation state +I, such as the organometallic fac-[Re(H2O)3(CO)3]+ are promising lead compounds compared to those with oxidation states +III and +V since they can be prepared under mild conditions and do not tend to reoxidize to oxidation state +VII while multidentate ligands can be attached under substitution of coordinated water molecules. This study comprises the application of the Free-Ion Selective Radiotracer Extraction (FISRE) technique in order to determine dissociation rate constants of complexes bearing the [188Re(CO)3]+-core at tracer levels in vitro with regards to their time-dependent kinetic speciation. As ligands, the tridentate l-histidine as well as the dipeptides l-carnosine (β-alanyl-l-histidine) and glycyl-l-histidine were chosen in order to study the effects of different moieties attached to the primary amine of l-histidine. (author)