title: Imaging of the muscarinic acetylcholine neuroreceptor in rats with the M2 selective agonist [18F]FP-TZTP.
abstract: BACKGROUND
  [(18)F]FP-TZTP is an M2 muscarinic subtype selective receptor-binding radiotracer used in vivo to image human and nonhuman primate brain following both bolus injection and infusion. In order to carry out repeated studies in rodents, the techniques developed for primates must be transferred to rodents with the same precision. This includes obtaining a metabolite-corrected input function.
  
  
  METHODS
  We compared bolus injection with constant infusion in rats that were awake or under isoflurane anesthesia. Brain-plasma and brain-blood distribution ratios were calculated by dividing brain (18)F concentrations, determined in vivo by positron emission tomography imaging with the Advanced Technology Laboratory Animal Scanner, ex vivo by direct counting in excised brain tissue or by quantitative autoradiography by the plasma or whole blood concentrations that had been corrected for metabolite contents.
  
  
  RESULTS
  Blood volume constraints prevented adequate blood sampling to define a precise input function after bolus injection, thus preventing full kinetic analysis. Constant infusion, however, required fewer blood samples to define the input function, allowing calculation of distribution ratios, but complete equilibrium between plasma and tissue had not yet been reached after 120 min.
  
  
  CONCLUSIONS
  Our results showed that the blood clearance and metabolism were too rapid to obtain a reproducible input function after bolus injection. The equilibrium distribution ratios did not lead to precise biochemical parameters, but the constant infusion was more suitable in that distribution ratios between tissue and plasma were statistically more precise. Constant infusion is the better approach for studying [(18)F]FP-TZTP by small animal imaging.
authors.affiliation: PET Department, CC/NIH, Bethesda, MD, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Ravasi
authors.forename: Joji
authors.initials: J
authors.lastname: Tokugawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakayama
authors.forename: Jurgen
authors.initials: J
authors.lastname: Seidel
authors.forename: Louis
authors.initials: L
authors.lastname: Sokoloff
authors.forename: William C
authors.initials: WC
authors.lastname: Eckelman
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000009:adverse effects; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007530:Isoflurane / Q000009:adverse effects; D008297:Male; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000378:metabolism; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D018685:Anesthetics, Inhalation; D005462:Fluorine Radioisotopes; D011725:Pyridines; D043585:Receptor, Muscarinic M2; D013844:Thiazoles; C115177:FP-TZTP; D007530:Isoflurane; D000109:Acetylcholine