Synthesis of a non‐peptidic PET tracer designed for α5β1 integrin receptor. (14th March 2014) - Monaco, Alessandra
Abstract 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. Copyright © 2014 John Wiley & Sons, Ltd.