TY - JOUR
T1 - Kinetic modeling of [ 18 F]VAT, a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non-human primate brain
AU - Jin, Hongjun
AU - Yue, Xuyi
AU - Liu, Hui
AU - Han, Junbin
AU - Flores, Hubert
AU - Su, Yi
AU - Parsons, Stanley M.
AU - Perlmutter, Joel S.
AU - Tu, Zhude
N1 - Publisher Copyright:
© 2018 International Society for Neurochemistry
PY - 2018/3
Y1 - 2018/3
N2 - Molecular imaging of vesicular acetylcholine transporter (VAChT) in the brain provides an important cholinergic biomarker for the pathophysiology and treatment of dementias including Alzheimer's disease. In this study, kinetics modeling methods were applied and compared for quantifying regional brain uptake of the VAChT-specific positron emission tomography radiotracer, ((−)-(1-(-8-(2-fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone) ([ 18 F]VAT) in macaques. Total volume distribution (V T ) estimates were compared for one-tissue compartment model (1TCM), two-tissue compartment model (2TCM), Logan graphic analysis (LoganAIF) and multiple linear analysis (MA1) with arterial blood input function using data from three macaques. Using the cerebellum-hemispheres as the reference region with data from seven macaques, three additional models were compared: reference tissue model (RTM), simplified RTM (SRTM), and Logan graphic analysis (LoganREF). Model selection criterion indicated that a) 2TCM and SRTM were the most appropriate kinetics models for [ 18 F]VAT; and b) SRTM was strongly correlated with 2TCM (Pearson's coefficients r > 0.93, p < 0.05). Test–retest studies demonstrated that [ 18 F]VAT has good reproducibility and reliability (TRV < 10%, ICC > 0.72). These studies demonstrate [ 18 F]VAT is a promising VAChT positron emission tomography tracer for quantitative assessment of VAChT levels in the brain of living subjects. (Figure presented.).
AB - Molecular imaging of vesicular acetylcholine transporter (VAChT) in the brain provides an important cholinergic biomarker for the pathophysiology and treatment of dementias including Alzheimer's disease. In this study, kinetics modeling methods were applied and compared for quantifying regional brain uptake of the VAChT-specific positron emission tomography radiotracer, ((−)-(1-(-8-(2-fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone) ([ 18 F]VAT) in macaques. Total volume distribution (V T ) estimates were compared for one-tissue compartment model (1TCM), two-tissue compartment model (2TCM), Logan graphic analysis (LoganAIF) and multiple linear analysis (MA1) with arterial blood input function using data from three macaques. Using the cerebellum-hemispheres as the reference region with data from seven macaques, three additional models were compared: reference tissue model (RTM), simplified RTM (SRTM), and Logan graphic analysis (LoganREF). Model selection criterion indicated that a) 2TCM and SRTM were the most appropriate kinetics models for [ 18 F]VAT; and b) SRTM was strongly correlated with 2TCM (Pearson's coefficients r > 0.93, p < 0.05). Test–retest studies demonstrated that [ 18 F]VAT has good reproducibility and reliability (TRV < 10%, ICC > 0.72). These studies demonstrate [ 18 F]VAT is a promising VAChT positron emission tomography tracer for quantitative assessment of VAChT levels in the brain of living subjects. (Figure presented.).
KW - [ F]VAT
KW - binding potential
KW - positron emission tomography
KW - tracer kinetic modeling
KW - vesicular acetylcholine transporter
UR - http://www.scopus.com/inward/record.url?scp=85044381100&partnerID=8YFLogxK
U2 - 10.1111/jnc.14291
DO - 10.1111/jnc.14291
M3 - Article
C2 - 29315563
AN - SCOPUS:85044381100
SN - 0022-3042
VL - 144
SP - 791
EP - 804
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 6
ER -