Kinetic modeling of [ 18 F]V AT , a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non‐human primate brain

Jin, Hongjun; Yue, Xuyi; Liu, Hui; Han, Junbin; Flores, Hubert; Su, Yi; Parsons, Stanley M.; Perlmutter, Joel S.; Tu, Zhude

doi:10.1111/jnc.14291

Title: Kinetic modeling of [ ¹⁸ F]V AT , a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non‐human primate brain

Journal Article · Sun Mar 25 00:00:00 EDT 2018 · Journal of Neurochemistry

DOI:https://doi.org/10.1111/jnc.14291· OSTI ID:1429541

Jin, Hongjun ^[1]; Yue, Xuyi ^[1]; Liu, Hui ^[1]; Han, Junbin ^[1]; Flores, Hubert ^[2]; Su, Yi ^[3]; Parsons, Stanley M. ^[4]; Perlmutter, Joel S. ^[5];

^[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

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

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Sponsoring Organization:: USDOE

Grant/Contract Number:: DES0012737

OSTI ID:: 1429541

Journal Information:: Journal of Neurochemistry, Journal Name: Journal of Neurochemistry Vol. 144 Journal Issue: 6; ISSN 0022-3042

Publisher:: Wiley-BlackwellCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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Cited by: 11 works

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Title: Kinetic modeling of [ ¹⁸ F]V AT , a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non‐human primate brain