title: Efficient 11C-carbonylation of isolated aryl palladium complexes for PET: application to challenging radiopharmaceutical synthesis.
abstract: We describe the successful implementation of palladium-aryl oxidative addition complexes as stoichiometric reagents in carbonylation reactions with (11)CO to produce structurally challenging, pharmaceutically relevant compounds. This method enables the first (11)C-carbonyl labeling of an approved PET tracer, [(11)C]raclopride, for the dopamine D2/D3 receptor by carbonylation with excellent radiochemical purity and yield. Two other molecules, [(11)C]olaparib and [(11)C]JNJ 31020028, were efficiently labeled in this manner. The technique distinguishes itself from existing methods by the markedly improved purity profiles of the tracer molecules produced and provides access to complex structures in synthetically useful yields, hereby offering a viable alternative to other (11)C-labeling strategies.
authors.affiliation: The Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry, Aarhus University , Gustav Wieds Vej 14, 8000 Aarhus, Denmark.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Andersen
authors.forename: Stig D
authors.initials: SD
authors.lastname: Friis
authors.forename: Hélène
authors.initials: H
authors.lastname: Audrain
authors.forename: Patrik
authors.initials: P
authors.lastname: Nordeman
authors.forename: Gunnar
authors.initials: G
authors.lastname: Antoni
authors.forename: Troels
authors.initials: T
authors.lastname: Skrydstrup
mesh_terms: D001549:Benzamides / Q000737:chemistry; D002250:Carbon Radioisotopes / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry*; D008958:Models, Molecular; D010165:Palladium / Q000737:chemistry*; D010793:Phthalazines / Q000737:chemistry; D010879:Piperazines / Q000737:chemistry; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D001549:Benzamides; D002250:Carbon Radioisotopes; D056831:Coordination Complexes; C547250:JNJ-31020028; D010793:Phthalazines; D010879:Piperazines; D019275:Radiopharmaceuticals; D020891:Raclopride; D010165:Palladium; C531550:olaparib