Preparation and Preliminary Evaluation of a Promising 99mTc-Labeled Isonitrile-Containing 6-Thia-Fatty Acid Derivative for Myocardial Metabolism Imaging.

ABSTRACT

For over 40 years, none of the previous 99mTc-labeled fatty acids for myocardial imaging has potential clinical use. 99mTc-(C10-6-thia-CO2H)(MIBI)5 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 [123I]BMIPP and were higher than or close to those of 99mTc-MIBI at 60 and 120 min. Most of 99mTc-(C10-6-thia-CO2H)(MIBI)5 was partially ß-oxidized to protein-bound metabolites in myocardium. Administration of trimetazidine dihydrochloride (TMZ, a fatty acid ß-oxidation inhibitor) to rats caused 51% reduction in the myocardial uptake of 99mTc-(C10-6-thia-CO2H)(MIBI)5 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 ß-oxidation.