Kinetic Evaluation and Test-retest Reproducibility of [C]UCB-J, a Novel Radioligand for Positron Emission Tomography Imaging of Synaptic Vesicle Glycoprotein 2A in Humans

Overview

Journal J Cereb Blood Flow Metab

Publisher Sage Publications

Specialties Cardiology & Vascular Diseases
Endocrinology
Neurology

Date 2017 Aug 10

PMID 28792356

Citations 111

Authors

Sjoerd J Finnema

Nabeel B Nabulsi

Joel Mercier

Shu-Fei Lin

Ming-Kai Chen

David Matuskey

Jean-Dominique Gallezot

Shannan Henry

Jonas Hannestad

Yiyun Huang

Richard E Carson

Affiliations

Soon will be listed here.

Abstract

Synaptic vesicle glycoprotein 2A (SV2A) is ubiquitously present in presynaptic terminals. Here we report kinetic modeling and test-retest reproducibility assessment of the SV2A positron emission tomography (PET) radioligand [C]UCB-J in humans. Five volunteers were examined twice on the HRRT after bolus injection of [C]UCB-J. Arterial blood samples were collected for measurements of radiometabolites and free fraction. Regional time-activity curves were analyzed with 1-tissue (1T) and 2-tissue (2T) compartment models to estimate volumes of distribution ( V). Parametric maps were generated using the 1T model. [C]UCB-J metabolized fairly quickly, with parent fraction of 36 ± 13% at 15 min after injection. Plasma free fraction was 32 ± 1%. Regional time-activity curves displayed rapid kinetics and were well described by the 1T model, except for the cerebellum and hippocampus. V values estimated with the 2T model were similar to 1T values. Parametric maps were of high quality and V values correlated well with time activity curve (TAC)-based estimates. Shortening of acquisition time from 120 min to 60 min had a negligible effect on V values. The mean absolute test-retest reproducibility for V was 3-9% across regions. In conclusion, [C]UCB-J exhibited excellent PET tracer characteristics and has potential as a general purpose tool for measuring synaptic density in neurodegenerative disorders.

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