Synthesis, radiolabeling and evaluation of a new positively charged ~(99m)Tc-labeled fatty acid derivative for myocardial imaging

摘要

~(123)I-Iabeled fatty acids and ~(18)F-FDG are used as metabolic markers for detecting myocardial abnormalities. However, a ~(99m)Tc-based molecule may find wider application. In the present work, a new ~(99m)Tc-labeled, uni-positively charged, 16-carbon fatty acid has been prepared and evaluated in normal Swiss mice. The results are then compared with the neutral analogue reported earlier. A 16-cysteinyl hexadecanoic acid conjugate was synthesized in a six-step synthetic procedure starting with 16-bromohexadecanoic acid. The ligand upon incubation with [~(99m)TcN(PNP6)]~(2+) core formed the required positively charged complex in approx 85% yield. The complex, which was obtained as a mixture of syn-anti isomers, was purified by HPLC and the major fraction was used for in vivo studies in Swiss mice. The biodistribution studies in Swiss mice showed initial uptake similar to ~(125)I-IPPA followed by rapid clearance from the myocardium till 10 min p.i. Thereafter, the rate of clearance was significantly decreased, an observation reported earlier for positively charged fatty acid complexes. In terms of absolute uptake, the positively charged complex performed better than the neutral analogue reported earlier. The positively charged fatty acid complexes, prepared using [~(99m)TcN(PNP)]~(2+) core, seems to be better candidates for the development of myocardial metabolic tracers than their neutral counterparts.