title: Development of new radiopharmaceuticals for imaging monoamine oxidase B.
abstract: BACKGROUND
  Imaging monoamine oxidase B (MAO-B) in the central nervous system with PET is an important goal for psychiatric studies. We here report an improved and automated radiosynthesis of N-(6-[(18)F]-fluorohexyl)-N-methylpropargylamine ([(18)F]FHMP; [(18)F]-1), as well as the radiosynthesis of two new promising candidates for imaging cerebral MAO-B, namely, carbon-11-labeled 3-(4-[(11)C]-methoxyphenyl)-6-methyl-2H-1-benzopyran-2-one ([(11)C]-2) and N-((1H-pyrrol-2-yl)methyl)-N-[(11)C]-methyl-1-phenylmethanamine ([(11)C]-3).
  
  
  METHODS
  Fluorine-18-labeled 1 was prepared via a tosyloxy precursor in 29%±5% uncorrected radiochemical yield, relative to [(18)F]-fluoride. Both carbon-11-labeled compounds were prepared with [(11)C]CH(3)I using the "LOOP" method in 11% and 18% uncorrected radiochemical yields, respectively, relative to starting [(11)C]CO(2). All radiotracers had specific activities >37 GBq/μmol and were >98% radiochemically pure at end of synthesis (<40 min). All radiotracers were evaluated by ex vivo biodistribution studies in conscious rodents.
  
  
  RESULTS
  A major radioactive metabolite in the rodent brain was observed following administration of [(18)F]-1. While [(11)C]-2 had moderate brain penetration and good clearance from normal brain tissue, distribution of radioactivity in brain was indicative of free and nonspecific binding. Good brain uptake was observed with [(11)C]-3 (0.8%-1.4% injected dose per gram at 5 min postinjection), binding appeared to be reversible and distribution conformed with regional distribution of MAO-B in the rat brain. Preinjection of 3 or L-deprenyl showed a modest reduction (up to 25%) of brain activity.
  
  
  CONCLUSIONS
  Carbon-11-labeled 3 was found to have the most favorable properties of the radiotracers evaluated; however, the signal-to-noise ratio was too low to warrant further in vivo imaging studies. Alternative radiotracers for imaging MAO-B are under development.
authors: PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada M5T 1R8. neil.vasdev@utoronto.ca
authors: Neil
authors: N
authors: Vasdev
authors: Oleg
authors: O
authors: Sadovski
authors: Matthew D
authors: MD
authors: Moran
authors: Jun
authors: J
authors: Parkes
authors: Jeffrey H
authors: JH
authors: Meyer
authors: Sylvain
authors: S
authors: Houle
authors: Alan A
authors: AA
authors: Wilson
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D008995:Monoamine Oxidase / Q000378:metabolism*; D010880:Piperidines / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D019275:Radiopharmaceuticals / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C453539:4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D010880:Piperidines; D019275:Radiopharmaceuticals; D008995:Monoamine Oxidase