TY - JOUR
T1 - Mass dose effects and in vivo affinity in brain PET receptor studies--a study of cerebral 5-HT4 receptor binding with [11C]SB207145
AU - Madsen, Karine
AU - Marner, Lisbeth
AU - Haahr, Mette
AU - Gillings, Nicolas
AU - Knudsen, Gitte M
N1 - Copyright © 2011 Elsevier Inc. All rights reserved.
PY - 2011/11
Y1 - 2011/11
N2 - 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 [ 11C]SB207145, a new PET radioligand for imaging the cerebral 5-HT 4 receptors in humans. Test-retest PET studies with varying specific activities of [ 11C]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.
AB - 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 [ 11C]SB207145, a new PET radioligand for imaging the cerebral 5-HT 4 receptors in humans. Test-retest PET studies with varying specific activities of [ 11C]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.
U2 - 10.1016/j.nucmedbio.2011.04.006
DO - 10.1016/j.nucmedbio.2011.04.006
M3 - Journal article
SN - 0969-8051
VL - 38
SP - 1085
EP - 1091
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 8
ER -