Preparation of highly specific radioactivity [ 18F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography

• Published in: Nuclear medicine and biology Vol. 32; no. 2; pp. 109 - 116
• Main Authors: Ryzhikov, Nikolaj N., Seneca, Nicholas, Krasikova, Raisa N., Gomzina, Natalia A., Shchukin, Evgeny, Fedorova, Olga S., Vassiliev, Dmitrij A., Gulyás, Balázs, Hall, Håkan, Savic, Ivanka, Halldin, Christer
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2005
• Subjects: [ 18F]Flumazenil; Animals; Brain; Brain - diagnostic imaging; Brain - metabolism; Central benzodiazepine receptors; Flumazenil - analogs & derivatives; Flumazenil - chemistry; Flumazenil - pharmacokinetics; Humans; In Vitro Techniques; Isotope Labeling - methods; Macaca fascicularis; Medicin och hälsovetenskap; Metabolic Clearance Rate; Nucleophilic fluorination; Organ Specificity; PET; Positron-Emission Tomography - methods; Radiation Dosage; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Receptors, GABA-A - metabolism; Ro 15-1788; Tissue Distribution; Brain; Central benzodiazepine receptors; [ 18F]Flumazenil; Nucleophilic fluorination; PET; Ro 15-1788
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2004.11.001

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 K 18F/kryptofix complex in DMF at 160°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.