title: The radiosynthesis of [18F]PK 14105 as an alternative radioligand for peripheral type benzodiazepine binding sites.
abstract: A method has been developed for labelling PK 14105 [N-methyl-N-(1-methyl-propyl)-1(2-fluoro-5-nitrophenyl)isoquinoline-3- carboxamide], a ligand that has high affinity and selectivity for peripheral type benzodiazepine binding sites (PBBS), with NCA fluorine-18 (t1/2 = 109.8 min, beta + = 96.9%). The method involves treating the 2-chloro-analogue with cyclotron-produced NCA [18F]fluoride in dimethyl sulphoxide, with rubidium carbonate as base, at 140 degrees C for 20 min. Purification is achieved by separation on a reverse phase Sep-Pak followed by PHLC on a silica gel column, to give chemically and radiochemically pure product with a specific activity of ca 7.4 GBq/mumol (200 mCi/mumol), decay-corrected to the end of radionuclide production (EOB). The radiosynthesis requires 210 min. giving a radiochemical yield of 10-20%, decay-corrected to EOB. [18F]PK 14105 was found to bind avidly to sites associated with kainic acid-induced unilateral lesions of rat striata. Such binding was blocked by pre-dosing the rat with PK 11195, so providing evidence for specific binding to PBBS. These results suggest that [18F]PK 14105 has potential for studying phenomena associated with PBBS in man by PET.
authors.affiliation: MRC Cyclotron Unit, Hammersmith Hospital, London, U.K.
authors.forename: C
authors.initials: C
authors.lastname: Pascali
authors.forename: S K
authors.initials: SK
authors.lastname: Luthra
authors.forename: V W
authors.initials: VW
authors.lastname: Pike
authors.forename: G W
authors.initials: GW
authors.lastname: Price
authors.forename: R G
authors.initials: RG
authors.lastname: Ahier
authors.forename: S P
authors.initials: SP
authors.lastname: Hume
authors.forename: R
authors.initials: R
authors.lastname: Myers
authors.forename: L
authors.initials: L
authors.lastname: Manjil
authors.forename: J E
authors.initials: JE
authors.lastname: Cremer
mesh_terms: D000818:Animals; D001665:Binding Sites; D003342:Corpus Striatum / Q000187:drug effects; D005462:Fluorine Radioisotopes; D007546:Isoquinolines; D007553:Isotope Labeling / Q000379:methods; D007608:Kainic Acid; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism / Q000494:pharmacology
chemical_list: D005462:Fluorine Radioisotopes; D007546:Isoquinolines; D011963:Receptors, GABA-A; D007608:Kainic Acid; C051238:PK 14105