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Synthesis of a non‐peptidic PET tracer designed for α 5 β 1 integrin receptor
Author(s) -
Monaco Alessandra,
Michelin Olivier,
Prior John,
Rüegg Curzio,
Scapozza Leonardo,
Seimbille Yann
Publication year - 2014
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3190
Subject(s) - chemistry , cycloaddition , azide , alkyne , integrin , yield (engineering) , receptor , stereochemistry , click chemistry , pet imaging , radiochemistry , combinatorial chemistry , organic chemistry , positron emission tomography , nuclear medicine , catalysis , biochemistry , medicine , materials science , metallurgy
Arginine–glycine–aspartic acid (RGD)‐containing peptides have been traditionally used as PET probes to noninvasively image angiogenesis, but recently, small selective molecules for α 5 β 1 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 α 5 β 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‐[ 18 F]fluoroethane ([ 18 F]12). Different reaction conditions between PMt and [ 18 F]12 were investigated, but all of them afforded [ 18 F]FPMt in 15 min with similar radiochemical yields (80–83%, decay corrected). Overall, the final radiopharmaceutical ([ 18 F]FPMt) was obtained after a synthesis time of 60–70 min in 42–44% decay‐corrected radiochemical yield. Copyright © 2014 John Wiley & Sons, Ltd.