Cysteine Derivatized Tc-99m-Labelled Fatty Acids As Beta-Oxidation Markers

With the aim of developing Tc-99m-labeled fatty acids intended for myocardial metabolism imaging we report herein the synthesis and characterization of two novel derivatives of undecanonoic and hexadecanonoic acid that have been functionalized at the omega-site by cysteine through the formation of a thioether bond (Cys-FA11 and Cys-FA16). Equimolar amounts of each ligand and the [NEt4](2)[Re(CO)(3)Br-3] precursor generated the respective hexacoordinated neutral complexes in which the ligand coordinated to the metal through the SNO donor system of cysteine. The rhenium complexes were characterized by elemental analysis, IR and NMR spectroscopies. The analogous technetium-99m complexes, Tc-99m-Cys-FA11 and Tc-99m-Cys-FA16 were prepared by incubation of the ligand with the precursor [Tc-99m(CO)(3)(H2O)(3)](+) (radiochemical yield >= 98%). Their structure was established by comparative HPLC techniques. In vivo studies in mice showed high initial heart uptake for both Tc-99m complexes (7.4 +/- 0.53 and 7.07 +/- 0.73 percentage of injected dose (%ID)/g at 1 min post injection. Rapid clearance (0.60 +/- 0.02 %ID/g) was observed for Tc-99m-Cys-FA11 while the clearance of the longer fatty acid Tc-99m-Cys-FA16 was slower (2.31 +/- 0.09 %ID/g at 15 min p.i.). Metabolite analysis study indicated that complexes were catabolized through the beta-oxidation process.