title: [11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats.
abstract: BACKGROUND
  At present, several positron emission tomography (PET) tracers are in use for imaging P-glycoprotein (P-gp) function in man. At baseline, substrate tracers such as R-[11C]verapamil display low brain concentrations with a distribution volume of around 1. [11C]phenytoin is supposed to be a weaker P-gp substrate, which may lead to higher brain concentrations at baseline. This could facilitate assessment of P-gp function when P-gp is upregulated. The purpose of this study was to synthesize [11C]phenytoin and to characterize its properties as a P-gp tracer.
  
  
  METHODS
  [11C]CO was used to synthesize [11C]phenytoin by rhodium-mediated carbonylation. Metabolism and, using PET, brain pharmacokinetics of [11C]phenytoin were studied in rats. Effects of P-gp function on [11C]phenytoin uptake were assessed using predosing with tariquidar.
  
  
  RESULTS
  [11C]phenytoin was synthesized via [11C]CO in an overall decay-corrected yield of 22 ± 4%. At 45 min after administration, 19% and 83% of radioactivity represented intact [11C]phenytoin in the plasma and brain, respectively. Compared with baseline, tariquidar predosing resulted in a 45% increase in the cerebral distribution volume of [11C]phenytoin.
  
  
  CONCLUSIONS
  Using [11C]CO, the radiosynthesis of [11C]phenytoin could be improved. [11C]phenytoin appeared to be a rather weak P-gp substrate.
authors: Department of Nuclear Medicine & PET Research, Radionuclide Centre, VU University Medical Center, P,O, box 7057, Amsterdam 1081, HV, The Netherlands. jverbeek@rnc.vu.nl.
authors: Joost
authors: J
authors: Verbeek
authors: Jonas
authors: J
authors: Eriksson
authors: Stina
authors: S
authors: Syvänen
authors: Maaike
authors: M
authors: Labots
authors: Elizabeth C M
authors: EC
authors: de Lange
authors: Rob A
authors: RA
authors: Voskuyl
authors: Martinus P J
authors: MP
authors: Mooijer
authors: Marissa
authors: M
authors: Rongen
authors: Adriaan A
authors: AA
authors: Lammertsma
authors: Albert D
authors: AD
authors: Windhorst