title: A practical synthesis of [(18) F]FtRGD: an angiogenesis biomarker for PET.
abstract: Integrins have become increasingly attractive targets for molecular imaging of angiogenesis with positron emission tomography or single-photon emission computed tomography, but the reliable production of radiopharmaceuticals remains challenging. A strategy for chemoselective labeling of the integrin ligand-c(RGDyK) peptide-has been developed on the basis of the Cu(I)-catalyzed conjugation reaction. Recently, we reported a nucleophilic detagging and fluorous solid-phase extraction method providing an easy way to implement an approach for obtaining 2-[(18) F]fluoroethyl azide. In this work, we report the practical use of this method for the preparation of the 2-[(18) F]fluoroethyl-triazolyl conjugated c(RGDyK) peptide: [(18) F]FtRGD. The two-step, two-pot synthesis, HPLC purification, and reformulation could be readily performed with a standard nucleophilic radiofluorination synthesizer (GE TRACERlab FXFN ), with minimal modifications. [(18) F]FtRGD was obtained in a solution for injection (>500 MBq/mL) in 10-30% nondecay-corrected radiochemical yield, excellent radiochemical purity (>98%), and 28 ± 13 GBq/µmol specific activity. [(18) F]FtRGD (Ki  = 54 ± 14 nM for αV β3 and 1.7 ± 0.2 nM for αV β5 ) was evaluated in mice and showed good stability in vivo, good tumor-to-background ratio (1.6 ± 0.3 %ID/g at 1.5 h post-injection in U87-MG tumors), and rapid urinary excretion. Therefore, [(18) F]FtRGD proved valuable for preclinical positron emission tomography imaging of integrin expression.
authors.affiliation: Singapore Bioimaging Consortium (A*STAR), Helios, 02-02, 11 Biopolis Way, Singapore, 138667, Singapore.
authors.forename: Romain
authors.initials: R
authors.lastname: Bejot
authors.forename: Julian
authors.initials: J
authors.lastname: Goggi
authors.forename: Shebbrin S
authors.initials: SS
authors.lastname: Moonshi
authors.forename: Edward G
authors.initials: EG
authors.lastname: Robins
mesh_terms: D000818:Animals; D008024:Ligands; D051379:Mice; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014230:Triazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics
chemical_list: C000589730:3-(1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)propanoic c(RGDyK); C515149:4-fluorobenozyl-glutamyl-cyclo(arginyl-glycyl-aspartyl-tyrosyl-lysyl)2; D008024:Ligands; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D014230:Triazoles
keywords: CuAAC; F-18; PET; RGD; angiogenesis; fluorous; integrins