Synthesis of a non‐peptidic PET tracer designed for α5β1 integrin receptor. (14th March 2014)

• Record Type: Journal Article
• Authors: Monaco, Alessandra; Michelin, Olivier; Prior, John; Rüegg, Curzio; Scapozza, Leonardo; Seimbille, Yann
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 57:Number 5(2014)
• Page Start: 365
• Page End: 370
• Publication Date: 2014-03-14
• Subjects: Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3190
• Languages: English
• ISSNs: 0362-4803

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Arginine–glycine–aspartic acid (RGD)‐containing peptides have been traditionally used as PET probes to noninvasively image angiogenesis, but recently, small selective molecules for <italic>α</italic>₅<italic>β</italic>₁ integrin receptor have been developed with promising results. Sixty‐one antagonists were screened, and <italic>tert</italic>‐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 <italic>α</italic>₅<italic>β</italic>₁ 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 &amp; Sons, Ltd.</p> </abstract>