One Step Radiosynthesis of 6-[18F]Fluoronicotinic Acid 2,3,5,6-Tetrafluorophenyl Ester ([18F]F-Py-TFP): A New Prosthetic Group for Efficient Labeling of Biomolecules with Fluorine-18

• Published in: Journal of medicinal chemistry Vol. 53; no. 4; pp. 1732 - 1740
• Main Authors: Olberg, Dag E, Arukwe, Joseph M, Grace, David, Hjelstuen, Ole K, Solbakken, Magne, Kindberg, Grete M, Cuthbertson, Alan
• Format: Journal Article
• Language: English
• Published: American Chemical Society 25-02-2010
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm9015813

The labeling of biomolecules for positron emission tomography (PET) with no-carrier-added fluorine-18 is almost exclusively accomplished using prosthetic groups in a two step procedure. The inherent complexity of the process renders full automation a challenge and leads to protracted synthesis times. Here we describe a new 18F-labeled prosthetic group based on nicotinic acid tetrafluorophenyl ester. Reaction of [18F]fluoride at 40 °C with the trimethylammonium precursor afforded 6-[18F]fluoronicotinic acid tetrafluorophenyl ester ([18F]F-Py-TFP) directly in 60−70% yield. [18F]F-Py-TFP was conveniently purified by Sep-Pak cartridge prior to incubation with a peptide containing the RGD sequence. The desired conjugate was formed rapidly and in good yields. An in vitro receptor-binding assay for the integrin αvβ3 was established to explore competition with peptide and peptidomimetic prepared from F-Py-TFP with 125I-echistatin. The nonradioactive conjugates were found to possess high binding affinities with calculated K i values in the low nanomolar range.