title: Preparation of highly specific radioactivity [18F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography.
abstract: A straightforward method for the preparation of no-carrier-added (n.c.a.) [18F]flumazenil via standard nucleophilic radiofluorination of the corresponding nitro-analog Ro 15-2344 has been developed. The labeling was performed by employing the K18F/kryptofix complex in DMF at 160 degrees C for 30 min and equimolar ratio [K/K2.2.2]+18F-/precursor. Under these conditions, an 18F incorporation rate into flumazenil was in the range of 55-60%. The final product was isolated by HPLC purification within a total synthesis time of 75 min and a radiochemical yield of about 30% (EOB). Human post-mortem whole-hemisphere autoradiography of brain sections demonstrated selective uptake of the radioligand in the areas of high density of the central benzodiazepine receptors (BZR). PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [18F]flumazenil as for [11C]flumazenil. In blocking experiments, almost all radioactivity was inhibited by the addition of unlabeled flumazenil. [18F]Flumazenil is a suitable radioligand for PET assessment of the BZR.
authors.affiliation: Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg, Russia.
authors.forename: Nikolaj N
authors.initials: NN
authors.lastname: Ryzhikov
authors.forename: Nicholas
authors.initials: N
authors.lastname: Seneca
authors.forename: Raisa N
authors.initials: RN
authors.lastname: Krasikova
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Gomzina
authors.forename: Evgeny
authors.initials: E
authors.lastname: Shchukin
authors.forename: Olga S
authors.initials: OS
authors.lastname: Fedorova
authors.forename: Dmitrij A
authors.initials: DA
authors.lastname: Vassiliev
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
authors.forename: Håkan
authors.initials: H
authors.lastname: Hall
authors.forename: Ivanka
authors.initials: I
authors.lastname: Savic
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005442:Flumazenil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D007553:Isotope Labeling / Q000379:methods; D008252:Macaca fascicularis; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011963:Receptors, GABA-A / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; C077354:5-(2'-fluoroethyl)flumazenil; D005442:Flumazenil