title: Synthesis of [18F]RGD-K5 by catalyzed [3 + 2] cycloaddition for imaging integrin αvβ3 expression in vivo.
abstract: In the last few years click chemistry reactions, and in particular copper-catalyzed cycloadditions have been used extensively for the preparation of new bioconjugated molecules such as (18)F-radiolabeled radiopharmaceuticals for positron emission tomography (PET). This study is focused on the synthesis of the Siemens imaging biomarker [(18)F]RGD-K5. This cyclic peptide contains an amino acid sequence which is a well known binding motif for integrin αvβ3 involved in cellular adhesion to the extracellular matrix. We developed an improved "click" chemistry method using Cu(I)-Monophos as catalyst to conjugate [(18)F]fluoropentyne to the RGD-azide precursor yielding [(18)F]RGD-K5. A comparison is made with the registered Siemens method with respect to synthesis, purification and quality control. [(18)F]RGD-K5 was obtained after 75 min overall synthesis time with an overall radiochemical yield of 35% (EOB). The radiochemical purity was >98% and the specific radioactivity was 100-200 GBq/μmol at the EOS.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. l.mirfeizi@umcg.nl
authors.forename: Leila
authors.initials: L
authors.lastname: Mirfeizi
authors.forename: Joe
authors.initials: J
authors.lastname: Walsh
authors.forename: Hartmuth
authors.initials: H
authors.lastname: Kolb
authors.forename: Lachlan
authors.initials: L
authors.lastname: Campbell-Verduyn
authors.forename: Rudi A
authors.initials: RA
authors.lastname: Dierckx
authors.forename: Ben L
authors.initials: BL
authors.lastname: Feringa
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
authors.forename: Tjibbe
authors.initials: T
authors.lastname: de Groot
authors.forename: Ivan
authors.initials: I
authors.lastname: Sannen
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Sofie
authors.initials: S
authors.lastname: Celen
mesh_terms: D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D005786:Gene Expression Regulation; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D049268:Positron-Emission Tomography; D011786:Quality Control; D011854:Radiochemistry / Q000379:methods*
chemical_list: C572955:18F-RGD-K5; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic