Synthesis and evaluation of novel technetium-99m(CO)₃-fatty acid derivatives prepared via "click chemistry" route as metabolic cardiac tracers

¹²³I-Iodophenylpentadecanoic acid (IPPA) is a clinical agent used for detecting metabolic cardiac abnormalities. Due to restricted availability of ¹²³I, there is a continued effort worldwide to develop a technetium-99m (^99mTc) substitute of this agent. The present work employs use of a well-known "click chemistry labeling" approach for incorporating ^99mTc to different fatty acids of variable chain lengths (8, 11, and 15 carbons) and evaluating them for cardiac imaging. ω- Bromo fatty acids (⁸C/¹¹C/¹⁵C) were synthetically modified at ω terminal to introduce a triazole ring-bearing glycine moiety in a five-step procedure. These were subsequently radiolabeled with preformed (^99mTc(CO)₃)+ synthon (prepared from carbonyl kit) under boiling water condition to yield the desired complexes. Biodistribution studies of the three complexes were performed in normal Swiss mice and results obtained compared with the standard *I-IPPA. Furthermore, in vitro activation of the ^99mTc-labeled tracer by acyl-CoA synthetase was performed to understand the true diagnostic potential. All the radiolabeled complexes were obtained with radiochemical purities >80% as determined by high-pressure liquid chromatography (HPLC). Biodistribution studies showed myocardial uptake of ~6%-9%ID/g nearly similar to*I-IPPA (~9% ID/g) for all the tracers at 2 min postinjection with significant retention up to 30 min (~1%-2% ID/g) but lower to the standard agent (~7% ID/g). Activation study of ¹⁵C fatty acid derivative with acyl-CoA synthetase (determined by HPLC) showed recognition of this complex by the enzyme. Significant uptake in myocardium and in vitro activation study shows that this "click" approach of ^99mTc incorporation holds potential for myocardial metabolic imaging. (author)