Preparation of highly specific radioactivity [18F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography.
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.
Ryzhikov
Nikolaj N
NN
Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg, Russia.
Seneca
Nicholas
N
Krasikova
Raisa N
RN
Gomzina
Natalia A
NA
Shchukin
Evgeny
E
Fedorova
Olga S
OS
Vassiliev
Dmitrij A
DA
Gulyás
Balázs
B
Hall
Håkan
H
Savic
Ivanka
I
Halldin
Christer
C
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
D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; C077354:5-(2'-fluoroethyl)flumazenil; D005442:Flumazenil