title: Suitability of [18F]altanserin and PET to determine 5-HT2A receptor availability in the rat brain: in vivo and in vitro validation of invasive and non-invasive kinetic models.
abstract: OBJECTIVE
  While the selective 5-hydroxytryptamine type 2a receptor (5-HT2AR) radiotracer [18F]altanserin is well established in humans, the present study evaluated its suitability for quantifying cerebral 5-HT2ARs with positron emission tomography (PET) in albino rats.
  
  
  METHODS
  Ten Sprague Dawley rats underwent 180 min PET scans with arterial blood sampling. Reference tissue methods were evaluated on the basis of invasive kinetic models with metabolite-corrected arterial input functions. In vivo 5-HT2AR quantification with PET was validated by in vitro autoradiographic saturation experiments in the same animals.
  
  
  RESULTS
  Overall brain uptake of [18F]altanserin was reliably quantified by invasive and non-invasive models with the cerebellum as reference region shown by linear correlation of outcome parameters. Unlike in humans, no lipophilic metabolites occurred so that brain activity derived solely from parent compound. PET data correlated very well with in vitro autoradiographic data of the same animals.
  
  
  CONCLUSIONS
  [18F]Altanserin PET is a reliable tool for in vivo quantification of 5-HT2AR availability in albino rats. Models based on both blood input and reference tissue describe radiotracer kinetics adequately. Low cerebral tracer uptake might, however, cause restrictions in experimental usage.
authors: Institute of Neuroscience and Medicine, INM-2, Forschungszentrum Jülich GmbH, Jülich, 52425, Germany. t.kroll@fz-juelich.de
authors: Tina
authors: T
authors: Kroll
authors: David
authors: D
authors: Elmenhorst
authors: Andreas
authors: A
authors: Matusch
authors: Franziska
authors: F
authors: Wedekind
authors: Angela
authors: A
authors: Weisshaupt
authors: Simone
authors: S
authors: Beer
authors: Andreas
authors: A
authors: Bauer
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging*; D002536:Cerebral Arteries / Q000000981:diagnostic imaging; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D007650:Ketanserin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D049268:Positron-Emission Tomography; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012044:Regression Analysis; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D044402:Receptor, Serotonin, 5-HT2A; C071983:altanserin; D007650:Ketanserin