Fluorine-18 click radiosynthesis and preclinical evaluation of a new 18F-labeled folic acid derivative

The folate receptor (FR) is highly expressed on most epithelial cancer cells, while normal cells show only restricted expression of FR. As a result, the FR is an ideal target for receptor-based molecular imaging and therapy of cancer and has become a promising target in oncology. To date, several folate-based chemotherapeutics and imaging probes such as radiopharmaceuticals for single photon emission computed tomography (SPECT) have been developed. However, an 18F-labeled folic acid derivative suitable for positron emission tomography (PET) imaging that can be routinely applied is still lacking. In this study, a new fluorinated and radiofluorinated folic acid derivative, 18/19F-click folate, was synthesized using click chemistry. In a convenient and very efficient two-step radiosynthesis, the isolated 18F-click folate was obtained in good radiochemical yields of 25−35% with a specific activity of 160 ± 70 GBq/μmol after ≤90 min synthesis time. The new compound was pharmacologically evaluated in vitro and ...