Automated synthesis and biodistribution study of cardiac fatty acid metabolism imaging agent 18F-FTHA

Abstract

Objective To achieve the fully automated synthesis of myocardial fatty acid metabolism imaging agent 14(R, S)-[18F]fluoro-6-thia-heptadecanoic acid (18F-FTHA), its biological distribution characteristics in normal Kunming mice were evaluated. Methods An automated synthesis module benzyl-14-tosyloxy-6-thia-heptadecanoate was used as precursor. The synthesis process was completed in four steps: nucleophilic substitution, alkaline hydrolysis, semi-preparative high-performance liquid chromatography, and solid-phase extraction. The physical(traits, activity, specific activity, half-life, and radionuclide purity), chemical (chemical purity, radiochemical purity, and room temperature stability), and biological properties (toxicity, sterility, and bacterial endotoxin) of the compound were identified. Twenty Kunming mice were randomly divided into four groups, with five mice in each group. The imaging agent 18F-FTHA 7.4 MBq(volume<0.2 mL) was injected through the tail vein. A group of mice was sacrificed at 15, 30, 60, and 90 min after injection, and the blood and main organs, such as heart, liver, spleen, lung, kidney, muscle, and bone, were obtained and weighed. The radioactivity count was measured by a gamma counter. The radioactive uptake(% ID/g) was calculated. Results The total synthesis time was about 50 min. The synthetic yield was(10.0±1.7)%. The 18F-FTHA is an injection containing 10% ethanol. The compound is a sterile, endotoxin-free, colorless clear solution. Its pH value is 6-7, specific activity is 65 GBq/mmol, radioactive nuclear purity is ≥99%, and radiochemical purity is >98%, which remained at >95% after 6 h at room temperature. Biodistribution experiments in normal Kunming mice showed that 18F-FTHA rapidly cleared in the blood, and a high myocardial uptake and low non-target organ uptake were observed. At 60 min after injection, the radioactivity uptake of myocardium, lungs, and liver reached(19.04 ± 4.87)%ID/g, (3.05 ± 0.52)%ID/g and(5.99 ± 2.96)%ID/g, respectively. The heart-to-lung and heart-to-liver uptake ratios totaled 6/1 and 3/1, respectively. The liver uptake at 15 and 30 min was slightly higher than the myocardial uptake. Conclusions The synthesis of 18F-FTHA, which features high radiochemical purity and good stability, has been automatically completed. Physical, chemical, and biological property identification results confirmed that the compound is safe and reliable. The biological distribution experiments on mice confirmed that myocardial uptake was higher than that of non-target organs. Thus, 18F-FTHA is suitable for experimental research. Key words: Cardiac metabolism; Fatty acid; Positron emission tomography; 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid; Biodistribution