Preparation and Preliminary Evaluation of a Promising ^99mTc-Labeled Isonitrile-Containing 6-Thia-Fatty Acid...

For over 40 years, none of the previous ^99mTc-labeled fatty acids for myocardial imaging has potential clinical use. Tc-(C10-6-thia-COH)(MIBI) is the first ^99mTc-labeled fatty acid to exhibit good myocardial uptake (2.06 ± 0.06%ID/g) at 60 min post injection, high heart-to-liver ratio (6.43 ± 1.85 and 9.68 ± 0.76), high heart-to-lung ratio (9.48 ± 1.39 and 11.02 ± 0.89), and high heart-to-blood ratio (164.01 ± 43.51 and 197.36 ± 32.29) at 60 and 120 min in Sprague-Dawley (SD) rats, respectively. It also demonstrated excellent myocardial imaging quality. The above target-to-nontarget ratios exceeded those of [I]BMIPP and were higher than or close to those of Tc-MIBI at 60 and 120 min. Most of Tc-(C10-6-thia-COH)(MIBI) was partially β-oxidized to protein-bound metabolites in myocardium. Administration of trimetazidine dihydrochloride (TMZ, a fatty acid β-oxidation inhibitor) to rats caused 51% reduction in the myocardial uptake of Tc-(C10-6-thia-COH)(MIBI) and 61% reduction in the distribution of ^99mTc-radioactivity in a residual tissue pellet at 60 min, indicating its considerable sensitivity to myocardial fatty acid β-oxidation.