title: The 5-HT1A Receptor PET Radioligand 11C-CUMI-101 Has Significant Binding to α1-Adrenoceptors in Human Cerebellum, Limiting Its Use as a Reference Region.
abstract: Prazosin, a potent and selective α1-adrenoceptor antagonist, displaces 25% of11C-CUMI-101 ([O-methyl-11C]2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione) binding in monkey cerebellum. We sought to estimate the percentage contamination of11C-CUMI-101 binding to α1-adrenoceptors in human cerebellum under in vivo conditions. In vitro receptor-binding techniques were used to measure α1-adrenoceptor density and the affinity of CUMI-101 for these receptors in human, monkey, and rat cerebellum.
  
  
  METHODS
  Binding potential (maximum number of binding sites × affinity [(1/dissociation constant]) was determined using in vitro homogenate binding assays in human, monkey, and rat cerebellum.3H-prazosin was used to determine the maximum number of binding sites, as well as the dissociation constant of3H-prazosin and the inhibition constant of CUMI-101.
  
  
  RESULTS
  α1-adrenoceptor density and the affinity of CUMI-101 for these receptors were similar across species. Cerebellar binding potentials were 3.7 for humans, 2.3 for monkeys, and 3.4 for rats.
  
  
  CONCLUSIONS
  Reasoning by analogy, 25% of11C-CUMI-101 uptake in human cerebellum reflects binding to α1-adrenoceptors, suggesting that the cerebellum is of limited usefulness as a reference tissue for quantification in human studies.
authors: Molecular Imaging Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland stal.shrestha@nih.gov.
authors: Stal S
authors: SS
authors: Shrestha
authors: Molecular Imaging Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland.
authors: Jeih-San
authors: JS
authors: Liow
authors: Molecular Imaging Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland.
authors: Kimberly
authors: K
authors: Jenko
authors: Molecular Imaging Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland.
authors: Masamichi
authors: M
authors: Ikawa
authors: Molecular Imaging Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland.
authors: Sami S
authors: SS
authors: Zoghbi
authors: Molecular Imaging Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland.
authors: Robert B
authors: RB
authors: Innis
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000882:Haplorhini; D006801:Humans; D008024:Ligands; D010879:Piperazines / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000592:standards*; D011224:Prazosin / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012015:Reference Standards; D013696:Temperature; D014227:Triazines / Q000378:metabolism*
chemical_list: C529131:2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5-(2H,4H)-dione; D008024:Ligands; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D014227:Triazines; D044282:Receptor, Serotonin, 5-HT1A; D011224:Prazosin
keywords: 5-HT1A receptor; CUMI-101; autoradiography; cerebellum; cross-reactivity; α1-adrenoceptor