Synthesis and biological evaluation of 17-[131I]iodo-9-telluraheptadecanoic acid, a potential myocardial imaging agent

Abstract

A method has been developed for the preparation of terminal halogenated tellurium fatty acids (X-R-Te-R'-COOH). The synthesis and physical properties of 17-bromo- and 17-iodo-9-telluraheptadecanoic acid (17-iodo-9-THDA) are described. The radiohalogenated agents are of interest as a result of their expected pronounced and prolonged heart uptake and potential use for evaluation of regional myocardial fatty acid metabolism. Evaluation in rats indicates that the myocardial uptake of 17-[131I]iodo-9-telluraheptadecanoic acid (17-[131I]iodo-9-THDA) is accompanied by significant in vivo deiodination. A comparison of the heart uptake and deiodination of 17-[131I]iodo-9-THDA and 16-[131I]iodopalmitic acid has demonstrated a close similarity in blood levels of radioactivity and thyroid uptake of radioiodide after administration of these agents to rats. These data suggest that the mechanism of deiodination of terminal radioiodinated alkanoic acids primarily results from direct cleavage of the carbon-iodine bond and not from loss of radioiodine from the final catabolite.

Structure Dependence of Long-Chain [18F]Fluorothia Fatty Acids as Myocardial Fatty Acid Oxidation Probes

“…Several non-thia fatty acid analogs of palmitic acid labeled with 18 F and 11 C were studied and documented in literature 4, 19–23 . However, the fate of the radiolabel involves multiple catabolic and anabolic processes and requires complex kinetic models to derive an estimate for FAO 4,19,20–24 . All the radiotracers in the current study were radiolabeled with 18 F at the terminal (ω) position, a site known to undergo metabolic defluorination in liver 25 .…”

Synthesis and Preliminary Evaluation of 18-18F-Fluoro-4-Thia-Oleate as a PET Probe of Fatty Acid Oxidation

“…Various branched-chain fatty acid analogs have been developed as metabolically retained probes (29,30), but they are poorly accepted for transport into the mitochondrion through CPT-I (31), rendering them sensitive for the indication of extramitochondrial lipid incorporation processes but not sensitive for the indication of FAO. Our approach of sulfur substitution (16) followed earlier work with larger heteroatom substituents (32). It was established that the sulfur substitution greatly diminishes the incorporation of fatty acids into complex lipids (33), rendering its kinetics more specific to mitochondrial metabolism.…”

No-Carrier-Added Radiohalogenation Methods with Heavy Halogens

“…[ have been proposed for aliphatic nucleophilic substitution. As mentioned, the tosylate group was successfully used for iodination of heptadecanoic acid [49,50], but failed in other cases [54]. Organic leaving groups have been successfully used to prepare 12S Ι-Δ 8 -tetrahydrocannabinol via the tosylate [55], and 77 Br-and I25 Inorhexestrol via the triflate [56], with specific activities of > 1600 Ci/mmole and 130 Ci/mmole, respectively.…”