Validation and test\u2013retest repeatability performance of parametric methods for [11C]UCB-J PET

Hayel Tuncel,David Vállez García,Marijke Den Hollander-Meeuwsen,Berkley A Lynch,Patrick Schober,Philip Scheltens,Joanne Ryan ,Bart N.m Van Berckel ,Andor W J M Glaudemans ,Erik F J De Vries,Sander C.j Verfaillie ,Steven Sweeney ,Emma M Coomans,Peter Paul De Deyn ,Ronald Boellaard,E.ch Wolters ,Albert D Windhorst,Robert C Schuit,Paula Kopschina Feltes,Magnus Ivarsson,Sandeep S.v Golla

doi:10.1186/s13550-021-00874-8

Abstract

[11C]UCB-J is a PET radioligand that binds to the presynaptic vesicle glycoprotein 2A. Therefore, [11C]UCB-J PET may serve as an in vivo marker of synaptic integrity. The main objective of this study was to evaluate the quantitative accuracy and the 28-day test–retest repeatability (TRT) of various parametric quantitative methods for dynamic [11C]UCB-J studies in Alzheimer’s disease (AD) patients and healthy controls (HC). Eight HCs and seven AD patients underwent two 60-min dynamic [11C]UCB-J PET scans with arterial sampling over a 28-day interval. Several plasma-input based and reference-region based parametric methods were used to generate parametric images using metabolite corrected plasma activity as input function or white matter semi-ovale as reference region. Different parametric outcomes were compared regionally with corresponding non-linear regression (NLR) estimates. Furthermore, the 28-day TRT was assessed for all parametric methods. Spectral analysis (SA) and Logan graphical analysis showed high correlations with NLR estimates. Receptor parametric mapping (RPM) and simplified reference tissue model 2 (SRTM2) BPND, and reference Logan (RLogan) distribution volume ratio (DVR) regional estimates correlated well with plasma-input derived DVR and SRTM BPND. Among the multilinear reference tissue model (MRTM) methods, MRTM1 had the best correspondence with DVR and SRTM BPND. Among the parametric methods evaluated, spectral analysis (SA) and SRTM2 were the best plasma-input and reference tissue methods, respectively, to obtain quantitatively accurate and repeatable parametric images for dynamic [11C]UCB-J PET.

Highlights

Abnormal brain deposits of amyloid β (Aβ), aggregation of tau into neurofibrillary tangles (NFTs) and synaptic loss are neuropathological hallmarks of Alzheimer’s disease (AD) [1]
Since synaptic vesicle protein 2A (SV2A) is highly expressed throughout the brain, it is a suitable target for positron emission tomography (PET) imaging when aiming to assess synaptic integrity in vivo
Total volume of distribution (VT) derived from Plasma input Logan (Logan) and spectral analysis (SA) are presented in Fig. 1a, separately for a typical AD and healthy controls (HC) subject

Summary

Introduction

Abnormal brain deposits of amyloid β (Aβ), aggregation of tau into neurofibrillary tangles (NFTs) and synaptic loss are neuropathological hallmarks of Alzheimer’s disease (AD) [1]. According to new AD models, the SV2A is a glycoprotein present in the membrane of presynaptic vesicles and is located in synapses. There are three different isoforms of synaptic vesicle proteins: SV2A, SV2B and SV2C [6]. SV2 proteins are involved in vesicle transport in the synapse and are essential for the function of our nervous system. The specific physiological role of SV2A is still unclear, SV2A is thought to be involved in the exocytosis of neurotransmitters and plays an important role in regulating/modulating synaptic function. Since SV2A is highly expressed throughout the brain, it is a suitable target for positron emission tomography (PET) imaging when aiming to assess synaptic integrity in vivo

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