Kinetic modeling of [ 18 F]V AT , a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non‐human primate brain
Abstract
Abstract Molecular imaging of vesicular acetylcholine transporter ( VACh T) 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 VACh T‐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]V AT ) in macaques. Total volume distribution ( V T ) estimates were compared for one‐tissue compartment model (1 TCM ), two‐tissue compartment model (2 TCM ), Logan graphic analysis (LoganA IF ) and multiple linear analysis (M A 1) 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 (Logan REF ). Model selection criterion indicated that a) 2 TCM and SRTM were the most appropriate kinetics models for [ 18 F]V AT ; and b) S RTM was strongly correlated with 2 TCM (Pearson's coefficients r > 0.93, p < 0.05). Test–retest studies demonstrated that [ 18 F]V AT has good reproducibility and reliability ( TRV < 10%, ICC > 0.72). These studies demonstrate [more »
- Authors:
-
[1]
- Department of Radiology Washington University School of Medicine St. Louis Missouri USA
- Department of Neurology Washington University School of Medicine St. Louis Missouri USA
- Department of Radiology Washington University School of Medicine St. Louis Missouri USA, Department of Neurology Washington University School of Medicine St. Louis Missouri USA
- Department of Chemistry and Biochemistry University of California Santa Barbara California USA
- Department of Radiology Washington University School of Medicine St. Louis Missouri USA, Department of Neurology Washington University School of Medicine St. Louis Missouri USA, Department of Neuroscience, Physical Therapy and Occupational Therapy Washington University School of Medicine St. Louis Missouri USA
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1429541
- Grant/Contract Number:
- DES0012737
- Resource Type:
- Publisher's Accepted Manuscript
- Journal Name:
- Journal of Neurochemistry
- Additional Journal Information:
- Journal Name: Journal of Neurochemistry Journal Volume: 144 Journal Issue: 6; Journal ID: ISSN 0022-3042
- Publisher:
- Wiley-Blackwell
- Country of Publication:
- United Kingdom
- Language:
- English
Citation Formats
Jin, Hongjun, Yue, Xuyi, Liu, Hui, Han, Junbin, Flores, Hubert, Su, Yi, Parsons, Stanley M., Perlmutter, Joel S., and Tu, Zhude. Kinetic modeling of [ 18 F]V AT , a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non‐human primate brain. United Kingdom: N. p., 2018.
Web. doi:10.1111/jnc.14291.
Jin, Hongjun, Yue, Xuyi, Liu, Hui, Han, Junbin, Flores, Hubert, Su, Yi, Parsons, Stanley M., Perlmutter, Joel S., & Tu, Zhude. Kinetic modeling of [ 18 F]V AT , a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non‐human primate brain. United Kingdom. https://doi.org/10.1111/jnc.14291
Jin, Hongjun, Yue, Xuyi, Liu, Hui, Han, Junbin, Flores, Hubert, Su, Yi, Parsons, Stanley M., Perlmutter, Joel S., and Tu, Zhude. Sun .
"Kinetic modeling of [ 18 F]V AT , a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non‐human primate brain". United Kingdom. https://doi.org/10.1111/jnc.14291.
@article{osti_1429541,
title = {Kinetic modeling of [ 18 F]V AT , a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non‐human primate brain},
author = {Jin, Hongjun and Yue, Xuyi and Liu, Hui and Han, Junbin and Flores, Hubert and Su, Yi and Parsons, Stanley M. and Perlmutter, Joel S. and Tu, Zhude},
abstractNote = {Abstract Molecular imaging of vesicular acetylcholine transporter ( VACh T) 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 VACh T‐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]V AT ) in macaques. Total volume distribution ( V T ) estimates were compared for one‐tissue compartment model (1 TCM ), two‐tissue compartment model (2 TCM ), Logan graphic analysis (LoganA IF ) and multiple linear analysis (M A 1) 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 (Logan REF ). Model selection criterion indicated that a) 2 TCM and SRTM were the most appropriate kinetics models for [ 18 F]V AT ; and b) S RTM was strongly correlated with 2 TCM (Pearson's coefficients r > 0.93, p < 0.05). Test–retest studies demonstrated that [ 18 F]V AT has good reproducibility and reliability ( TRV < 10%, ICC > 0.72). These studies demonstrate [ 18 F]V AT is a promising VACh T positron emission tomography tracer for quantitative assessment of VACh T levels in the brain of living subjects. image},
doi = {10.1111/jnc.14291},
journal = {Journal of Neurochemistry},
number = 6,
volume = 144,
place = {United Kingdom},
year = {Sun Mar 25 00:00:00 EDT 2018},
month = {Sun Mar 25 00:00:00 EDT 2018}
}
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