UNLABELLED: 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. CONCLUSION: The presented method for estimating the upper mass dose limit is suggested as part of validation of PET radioligands.
UNLABELLED: 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. CONCLUSION: The presented method for estimating the upper mass dose limit is suggested as part of validation of PET radioligands.
Authors: Stephen P H Alexander; Helen E Benson; Elena Faccenda; Adam J Pawson; Joanna L Sharman; Michael Spedding; John A Peters; Anthony J Harmar Journal: Br J Pharmacol Date: 2013-12 Impact factor: 8.739
Authors: Maxim E Sergeev; Mark Lazari; Federica Morgia; Jeffrey Collins; Muhammad Rashed Javed; Olga Sergeeva; Jason Jones; Michael E Phelps; Jason T Lee; Pei Yuin Keng; R Michael van Dam Journal: Commun Chem Date: 2018-03-22
Authors: Talakad G Lohith; Rong Xu; Tetsuya Tsujikawa; Cheryl L Morse; Kacey B Anderson; Robert L Gladding; Sami S Zoghbi; Masahiro Fujita; Robert B Innis; Victor W Pike Journal: Synapse Date: 2014-08-11 Impact factor: 2.562
Authors: Patrick M Fisher; Klaus K Holst; Dea Adamsen; Anders Bue Klein; Vibe G Frokjaer; Peter S Jensen; Claus Svarer; Nic Gillings; William F C Baare; Jens D Mikkelsen; Gitte M Knudsen Journal: Hum Brain Mapp Date: 2014-09-13 Impact factor: 5.038