Article (Scientific journals)
The pharmacokinetics of [(18)F]UCB-H revisited in the healthy non-human primate brain
Goutal, S; Guillermier, M; Becker, Guillaume et al.
2021In EJNMMI Res, 11 (1), p. 36
Peer reviewed
 

Files


Full Text
EJRE-D-20-00374_R2.pdf
Publisher postprint (2 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
synapses
Abstract :
[en] BACKGROUND: Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [(18)F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we evaluate the reliability of the three most commonly used modelling approaches for [(18)F]UCB-H in the non-human cynomolgus primate, adding the coupled fit of the non-displaceable distribution volume (VND) as an alternative approach to improve unstable fit. The results are discussed in the light of the current state of SV2A PET ligands. RESULTS: [(18)F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), although the model did not always converge (large total volume of distribution (VT) or large uncertainty of the estimate). 2TCM with coupled fit K1/k2 across brain regions stabilized the quantification, and confirmed a lower specific signal of [(18)F]UCB-H compared to the newest SV2A-ligands. However, the measures of VND and the influx parameter (K1) are similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [(19)F]UCB-H, demonstrating only 50% displacement of the total [(18)F]UCB-H signal at maximal occupancy of SV2A. As previously demonstrated in clinical studies, the graphical method of Logan provided a more robust estimate of VT with only a small bias compared to 2TCM. CONCLUSIONS: Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
Disciplines :
Neurology
Author, co-author :
Goutal, S
Guillermier, M
Becker, Guillaume ;  Université de Liège - ULiège > Département de Psychologie > Département de Psychologie
Gaudin, M
Bramoulle,, Y
Luxen, André ;  Université de Liège - ULiège > Département de chimie (sciences) > Département de chimie (sciences)
Lemaire, Christian ;  Université de Liège - ULiège > CRC In vivo Imaging-Radiochemistry
Plenevaux, Alain  ;  Université de Liège - ULiège > GIGA CRC In vivo Imaging - Preclinical Imaging
SALMON, Eric  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Centre de jour interdisciplinaire des troubles de la mémoire
Hantraye, P
Barret, O
Van Camp, N
Language :
English
Title :
The pharmacokinetics of [(18)F]UCB-H revisited in the healthy non-human primate brain
Publication date :
2021
Journal title :
EJNMMI Res
eISSN :
2191-219X
Volume :
11
Issue :
1
Pages :
36
Peer reviewed :
Peer reviewed
Available on ORBi :
since 01 May 2021

Statistics


Number of views
60 (3 by ULiège)
Number of downloads
3 (3 by ULiège)

Scopus citations®
 
4
Scopus citations®
without self-citations
4
OpenCitations
 
3

Bibliography


Similar publications



Contact ORBi