Technetium-99m-Labeled Long Chain Fatty Acid Analogues Metabolized by β-Oxidation in the Heart

The development of 99mTc-labeled fatty acid analogues metabolized by β-oxidation in the myocardium constitutes an unsolved challenge. On the basis of our recent findings that [188Re]tricarbonyl(cyclopentadienylcarbonate)rhenium ([188Re]CpTR-COOH) was recognized as an aromatic compound and was metabolized as such in the body, [99mTc]cyclopentadienyltricarbonyltechnetium ([99mTc]CpTT) was conjugated at the ω-position of pentadecanoic acid to prepare [99mTc]CpTT-PA. When injected into rats, [99mTc]CpTT-PA exhibited the maximum myocardial accumulation and heart-to-blood ratio of 3.85 %ID/g at 1 min and 4.60 at 10 min postinjection, respectively. The metabolic study using isolated Langendorff perfused rat hearts demonstrated that approximately 67% of perfused [99mTc]CpTT-PA was incorporated and [99mTc]CpTT-propionic acid, the metabolite after six cycles of β-oxidation of [99mTc]CpTT-PA, was detected as the major radiometabolite in the perfusate and myocardium. These findings indicate that [99mTc]CpTT-PA was recognized, transported, and metabolized as a long chain fatty acid analogue for energy production in the myocardium.