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

Journal of Nuclear Medicine

Shuyan Wang¹  Mukesh K. Pandey¹  Anthony P. Belanger¹  Timothy R. DeGrado¹  Falguni Bhattacharyya¹ 

关键词: fatty acid oxidation;    PET;    myocardial metabolism;   

DOI  :  10.2967/jnumed.109.074245

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Fatty acid oxidation (FAO) is a major energy-providing process with important implications in cardiovascular, oncologic, neurologic, and metabolic diseases. A novel 4-thia oleate analog, 18-18F-fluoro-4-thia-oleate (18F-FTO), was evaluated in relationship to the previously developed palmitate analog 16-18F-fluoro-4-thia-palmitate (18F-FTP) as an FAO probe. Methods: 18F-FTO was synthesized from a corresponding bromoester. Biodistribution and metabolite analysis studies were performed in rats. Preliminary small-animal PET studies were performed with 18F-FTO and 18F-FTP in rats. Results: A practical synthesis of 18F-FTO was developed, providing a radiotracer of high radiochemical purity (>99%). In fasted rats, myocardial uptake of 18F-FTO (0.70 ± 0.30% dose kg [body mass]/g [tissue mass]) was similar to that of 18F-FTP at 30 min after injection. At 2 h, myocardial uptake of 18F-FTO was maintained, whereas 18F-FTP uptake in the heart was 82% reduced. Similar to 18F-FTP, 18F-FTO uptake by the heart was approximately 80% reduced at 30 min by pretreatment of rats with the CPT-I inhibitor etomoxir. Folch-type extraction analyses showed 70–90% protein-bound fractions in the heart, liver, and skeletal muscle, consistent with efficient trafficking of 18F-FTO to the mitochondrion with subsequent metabolism to protein-bound species. Preliminary small-animal PET studies showed rapid blood clearance and avid extraction of 18F-FTO and of 18F-FTP into the heart and liver. Images of 18F-FTO accumulation in the rat myocardium were clearly superior to those of 18F-FTP. Conclusion: 18F-FTO is shown to be a promising metabolically trapped FAO probe that warrants further evaluation.

【 授权许可】

Unknown