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

Monaco, Alessandra; Michelin, Olivier; Prior, John; Rüegg, Curzio; Scapozza, Leonardo; Seimbille, Yann

doi:10.1002/jlcr.3190

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Journal article

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

Monaco, Alessandra Cyclotron Unit, University Hospital of Geneva, Switzerland - School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Switzerland
Michelin, Olivier Swiss Institute of Bioinformatics, University of Lausanne, Switzerland
Prior, John CHUV, Department of Nuclear Medicine, Lausanne, Switzerland
Rüegg, Curzio Faculty of Science, Department of Medicine, University of Fribourg, Switzerland
Scapozza, Leonardo School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Switzerland
Seimbille, Yann Cyclotron Unit, University Hospital of Geneva, Switzerland - School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Switzerland

01.03.2014

Published in:

Journal of labelled compounds & radiopharmaceuticals. - 2014, vol. 57, no. 5, p. 365-370

<em>α</em>₅<em>β</em>₁ integrin receptor

PET, 1-azide-2-[¹⁸F]fluoroethane

English 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.

Faculty

Faculté des sciences et de médecine

Department

Médecine 3ème année

Language