The radiosynthesis of [18F]PK 14105 as an alternative radioligand for peripheral type benzodiazepine binding sites

Int J Rad Appl Instrum A. 1990;41(5):477-82. doi: 10.1016/0883-2889(90)90008-5.

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.

MeSH terms

  • Animals
  • Binding Sites
  • Corpus Striatum / drug effects
  • Fluorine Radioisotopes*
  • Isoquinolines*
  • Isotope Labeling / methods
  • Kainic Acid
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, GABA-A* / metabolism
  • Receptors, GABA-A* / pharmacology

Substances

  • Fluorine Radioisotopes
  • Isoquinolines
  • Receptors, GABA-A
  • Kainic Acid
  • PK 14105