One step radiosynthesis of 6-[(18)F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester ([(18)F]F-Py-TFP): a new prosthetic group for efficient labeling of biomolecules with fluorine-18.
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 (18)F-labeled prosthetic group based on nicotinic acid tetrafluorophenyl ester. Reaction of [(18)F]fluoride at 40 degrees C with the trimethylammonium precursor afforded 6-[(18)F]fluoronicotinic acid tetrafluorophenyl ester ([(18)F]F-Py-TFP) directly in 60-70% yield. [(18)F]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 alpha(v)beta(3) was established to explore competition with peptide and peptidomimetic prepared from F-Py-TFP with (125)I-echistatin. The nonradioactive conjugates were found to possess high binding affinities with calculated K(i) values in the low nanomolar range.
Olberg
Dag E
DE
Department of Pharmaceutics and Biopharmaceutics, Institute of Pharmacy, University of Tromsø, N-9037 Tromsø, Norway. dag.erlend.olberg@petsenteret.no
Arukwe
Joseph M
JM
Grace
David
D
Hjelstuen
Ole K
OK
Solbakken
Magne
M
Kindberg
Grete M
GM
Cuthbertson
Alan
A
D001667:Binding, Competitive; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes; D006801:Humans; D066298:In Vitro Techniques; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007553:Isotope Labeling; D009539:Nicotinic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
C547953:6-fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester; D005462:Fluorine Radioisotopes; D039302:Integrin alphaVbeta3; D009539:Nicotinic Acids; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C047981:arginyl-glycyl-aspartic acid