Radiosynthesis and preclinical PET evaluation of [18F] fluoro-pivalic acid: a novel fatty acid metabolism tracer with potential for brain tumor imaging
摘要
The limitations of [18F] FDG PET in brain tumor imaging, due to its high physiological uptake in normal gray matter, underscore the need for novel, more specific radiotracers. Similar to the well-documented increase in glycolytic flux, many cancers, including gliomas, exhibit aberrant lipid metabolism. This study investigates the potential of [18F] fluoro-pivalic acid ([18F] FPIA), a short-chain, branched fatty acid analog, as a PET imaging agent for this pathway. We present its foundational preclinical evaluation to assess its suitability for future application in glioma detection. [18F] FPIA was synthesized via nucleophilic fluorination, and its chemical structure was confirmed by NMR spectroscopy. Radiosynthesis was optimized, and the final product was validated for radiochemical purity (> 99%) using radio-TLC. The preclinical profile of [18F] FPIA was evaluated through biodistribution studies and small-animal PET/CT imaging in normal Balb/c mice, with a comparative analysis to [18F] FDG. [18F] FPIA was reliably produced with a high chemical yield (80%) and excellent radiochemical purity. Biodistribution studies revealed significant tracer accumulation in the liver and kidneys, with minimal uptake in the healthy brain. PET imaging confirmed rapid clearance from the blood pool and high contrast in excretory organs. Notably, [18F] FPIA demonstrated significantly lower retention in the normal brain compared to [18F] FDG. We have successfully developed a robust method for the synthesis and radiolabeling of [18F] FPIA. The favorable preclinical profile, characterized by low background brain uptake and rapid systemic clearance, establishes [18F] FPIA as a promising PET radiotracer candidate. This foundational work justifies and provides a basis for its future evaluation for the specific targeting of gliomas via the fatty acid metabolism pathway.