Mass dose effects and in vivo affinity in brain PET receptor studies--a study of cerebral 5-HT4 receptor binding with [11C]SB207145

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 -