TY - JOUR
AU - Gröner, Benedikt
AU - Willmann, Michael
AU - Donnerstag, Lisa
AU - Urusova, Elizaveta
AU - Neumaier, Felix
AU - Humpert, Swen
AU - Endepols, Heike
AU - Neumaier, Bernd
AU - Zlatopolskiy, Boris D.
TI - 7-[18F]Fluoro-8-azaisatoic Anhydrides: Versatile Prosthetic Groups for the Preparation of PET Tracers
JO - Journal of medicinal chemistry
VL - 66
IS - 17
SN - 0095-9065
CY - Washington, DC
PB - ACS
M1 - FZJ-2023-03411
SP - 12629−12644
PY - 2023
AB - 18F-Fluorination of sensitive molecules is often challenging, but can be accomplished under suitably mild conditions using radiofluorinated prosthetic groups (PGs). Herein, 1-alkylamino-7-[18F]fluoro-8-azaisatoic anhydrides ([18F]AFAs) are introduced as versatile 18F-labeled building blocks that can be used as amine-reactive or “click chemistry” PGs. [18F]AFAs were efficiently prepared within 15 min by “on cartridge” radiolabeling of readily accessible trimethylammonium precursors. Conjugation with a range of amines afforded the corresponding 2-alkylamino-6-[18F]fluoronicotinamides in radiochemical conversions (RCCs) of 15−98%. In addition, radiolabeling of alkyne- or azide-functionalized precursors with azidopropyl- or propargyl-substituted [18F]AFAs using Cu-catalyzed click cycloaddition afforded the corresponding conjugates in RCCs of 44−88%. The practical utility of the PGs was confirmed by the preparation of three 18F-labeled PSMA ligands in radiochemical yields of 28−42%. Biological evaluation in rats demonstrated excellent in vivo stability of all three conjugates. In addition, one conjugate ([18F]JK-PSMA-15) showed favorable imaging properties for high-contrast visualization of small PSMA-positive lesions.
LB - PUB:(DE-HGF)16
C6 - 37625106
UR - <Go to ISI:>//WOS:001063590800001
DO - DOI:10.1021/acs.jmedchem.3c01310
UR - https://juser.fz-juelich.de/record/1014721
ER -