title: Mass dose effects and in vivo affinity in brain PET receptor studies--a study of cerebral 5-HT4 receptor binding with [11C]SB207145.
abstract: Attention to tracer dose principles is crucial in positron emission tomography (PET), and deviations can induce serious errors. In this study, we devise a method for determining receptor occupancy of the mass dose of the radioligand itself and the in vivo affinity.
  
  
  METHODS
  The approach was used for [(11)C]SB207145, a new PET radioligand for imaging the cerebral 5-HT(4) receptors in humans. Test-retest PET studies with varying specific activities of [(11)C]SB207145 were conducted in seven healthy subjects, and the output parameter regional BP(ND) was modeled. Individual occupancy plots were first computed to estimate the mass dose that saturates 50% of receptors (ID(50)), and subsequently, the maximal mass dose that can be injected (arbitrarily set at an occupancy <5%) was calculated. Scatchard plots were computed to estimate the in vivo K(D).
  
  
  RESULTS
  Increasing the mass dose resulted in a decrease in BP(ND), whilst the relative cerebellar uptake was unchanged. The ID(50) was 85.4±30.2 μg, and the upper mass dose limit was 4.5±1.6 μg, which does not require ultrahigh specific activity. The estimated in vivo K(D) was 2.8 nM (range 1.0-4.8), without any regional differences.
  
  
  CONCLUSIONS
  The presented method for estimating the upper mass dose limit is suggested as part of validation of PET radioligands.
authors.affiliation: Neurobiology Research Unit, The Neuroscience Center, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark. karine@nru.dk
authors.forename: Karine
authors.initials: K
authors.lastname: Madsen
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Marner
authors.forename: Mette
authors.initials: M
authors.lastname: Haahr
authors.forename: Nic
authors.initials: N
authors.lastname: Gillings
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D002250:Carbon Radioisotopes / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods; D044422:Receptors, Serotonin, 5-HT4 / Q000187:drug effects*; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D010880:Piperidines; C534709:SB 207145; D044422:Receptors, Serotonin, 5-HT4