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@article{Guo:2013:10.2967/jnumed.113.121020,
author = {Guo, Q and Colasanti, A and Owen, DR and Onega, M and Kamalakaran, A and Bennacef, I},
doi = {10.2967/jnumed.113.121020},
journal = {Journal of Nuclear Medicine},
pages = {1--9},
title = {Quantification of the Specific Translocator Protein Signal of18F-PBR111 in Healthy Humans: A Genetic PolymorphismEffect on In Vivo Binding},
url = {http://dx.doi.org/10.2967/jnumed.113.121020},
volume = {54},
year = {2013}
}

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TY  - JOUR
AB  - PET is used to image active inflammatory processes by targetingthe translocator protein (TSPO). In vitro, second-generation TSPOradioligands, such as PBR111, have been shown to bind to humantissue samples with either high affinity (high-affinity binders, HABs),low affinity (low-affinity binders, LABs), or an intermediate, mixedaffinity (mixed-affinity binders, MABs). We previously explainedthese differences in affinity in human tissue via the rs6971 polymorphismin the TSPO gene and predicted that the specific signalfrom PET ligands in vivo would vary accordingly. In silico modelingpredicted that 18F-PBR111 would have a moderate to high specificto-nonspecific ratio in the normal human brain. To test these predictions,we present here the analysis and modeling of 18F-PBR111data in healthy humans. Methods: Twenty-one subjects (9 HABs, 8MABs, and 4 LABs), 28–62 y old, genotyped for the rs6971 polymorphism,underwent 120-min PET scans with arterial samplingafter a bolus injection of 18F-PBR111. Compartmental models andLogan graphical methods enabled estimation of the total volume ofdistribution (VT) in regions of interest (ROIs). To evaluate the specificsignal, we developed 2 methods to estimate the nondisplaceablevolume of distribution (VND): the first assumed that the in vitro affinityratio of 18F-PBR111 in HABs relative to LABs (4-fold) is preserved invivo; the second modeled the difference in the HAB and MAB signalsin the context of an occupancy plot. Results: A 2-tissue-compartmentmodel described the data well, and a significant differencewas found between the VT of HABs, MABs, and LABs across allROIs examined (P , 0.05). We also found a significant correlationbetween VT and age for both HABs and MABs in most ROIs. Theaverage VND estimated by the 2 methods was 1.18 6 0.35 (methodI: VND 5 0.93, method II: VND 5 1.42), implying that the 18F-PBR111BPND was 2.78 6 0.46 in HABs, 1.48 6 0.28 in MABs, and 0.51 60.17 in LABs and that the in vivo affinity ratio was simil
AU  - Guo,Q
AU  - Colasanti,A
AU  - Owen,DR
AU  - Onega,M
AU  - Kamalakaran,A
AU  - Bennacef,I
DO  - 10.2967/jnumed.113.121020
EP  - 9
PY  - 2013///
SP  - 1
TI  - Quantification of the Specific Translocator Protein Signal of18F-PBR111 in Healthy Humans: A Genetic PolymorphismEffect on In Vivo Binding
T2  - Journal of Nuclear Medicine
UR  - http://dx.doi.org/10.2967/jnumed.113.121020
VL  - 54
ER  -

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