Synthesis of a non-peptidic PET tracer designed for α5β1 integrin receptor

摘要

Arginine–glycine–aspartic acid (RGD)-containing peptides have been traditionally used as PET probes to noninvasively image angiogenesis, but recently, small selective molecules for α5β1 integrin receptor have been developed with promising results. Sixty-one antagonists were screened, and tert-butyl (S)-3-(2-((3R,5S)-1-(3-(1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)propanoyl)-5-((pyridin-2-ylamino)methyl)pyrrolidin-3-yloxy)acetamido)-2-(2,4,6-trimethylbenzamido)propanoate (FPMt) was selected for the development of a PET tracer to image the expression of α5β1 integrin receptors. An alkynyl precursor (PMt) was initially synthesized in six steps, and its radiolabeling was performed according to the azide–alkyne copper(II)-catalyzed Huisgen's cycloaddition by using 1-azido-2-[18F]fluoroethane ([18F]12). Different reaction conditions between PMt and [18F]12 were investigated, but all of them afforded [18F]FPMt in 15?min with similar radiochemical yields (80–83%, decay corrected). Overall, the final radiopharmaceutical ([18F]FPMt) was obtained after a synthesis time of 60–70?min in 42–44% decay-corrected radiochemical yield.