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@INPROCEEDINGS{Foerges:1009675,
author = {Foerges, Anna Linea and Kroll, Tina and Matusch, Andreas
and Neumaier, Bernd and Bauer, Andreas and Drzezga,
Alexander and Elmenhorst, David},
title = {{Q}uantification of [18{F}]-{S}yn{V}es{T}-1 {PET} using
thin-layer chromatography and image derived input function},
reportid = {FZJ-2023-02928},
year = {2023},
abstract = {Objectives: Synaptic vesicle protein 2A, a marker of
synaptic density, can be imaged by [18F]SynVesT 1 positron
emission tomography (PET), but quantification requires an
arterial input function. An alternative to high-performance
liquid chromatography (HPLC) of arterial blood samples can
be an input function derived from the dynamic PET images in
combination with thin-layer chromatography (TLC)-based
analysis of arterialized venous blood. We aimed to quantify
synaptic density by obtaining an image derived input
function (IDIF) from bilateral internal carotid artery
volume of interest (VOI) at the level of the carotid siphon
and correcting it for metabolites using a newly developed
blood analysis with TLC.Methods: [18F]SynVesT-1 PET list
mode (90 min) data and three-dimensional T1-weighted
magnetic resonance (MR) data were collected in nine healthy
volunteers using an integrated 3 Tesla MR/BrainPET system.
Reconstructed PET data (framing schema: 6x 10s, 3x 20s, 3x
30s, 4x 60s, 3x 150s, 15x 300s) and corresponding MR data
were realigned, co-registered, segmented and normalized
using PMOD Neuro Tool. The first eight normalized PET frames
were averaged and filtered (6 mm 3D Gaussian), then, based
on this PET image, cubic VOIs were placed over the left and
right internal carotid arteries. Subsequently, the 20
hottest connected voxels within each cubic VOI were
automatically selected on each side and merged into one VOI,
which was transferred to the dynamic PET images to obtain
IDIF. Arterialized venous blood samples were collected
repeatedly during the PET scan. For blood analysis, aliquots
of plasma (400 µl) were mixed with SynVesT 1 cold standard
(20 µl, 5µg/ml) and extraction solution
(acetonitrile/methanol, 50/50, 800 µl). The mixture was
centrifuged and aliquots of supernatants were applied to a
TLC plate and developed with a mobile phase of
chloroform/methanol/diethylamine (18.4 ml/1.6 ml/40 µl).
Whole blood, plasma and pellets were measured in a
γ-counter. TLC plates were developed in a Canberra instant
imager for 4 h and analysed with the corresponding software.
IDIF was scaled [1] using whole blood samples drawn 60, 75
and 90 min after simultaneous injection and scan start to
correct for partial volume effects. The scaled IDIF was used
to generate a metabolite- and extraction-corrected (derived
from blood analysis) plasma input function. These input
functions were used to apply the one-tissue compartment
model (1TCM) to quantify regional synaptic density in the
human brain.Results: Synaptic density was quantified in nine
volunteers (4 females) aged 20-45 years (mean: 27.8 ± 9.4)
using TLC-based blood analysis, IDIF and the 1TCM. The
fraction of radioactivity corresponding to the parent
compound was 34 ± 6 $\%$ and 31 ± 5 $\%$ at 60 min and 90
min after radiotracer injection, respectively. The scaling
factor was 1.27 ± 0.20 on average. Mean [18F]SynVesT 1 VT
values ranged from 3.64 ± 21.06 mL/cm³ in the centrum
semiovale to 20.90 ± 3.87 ml/cm³ in the Heschl’s gyrus.
Estimated K1 ranged from 0.303 ±0.065 ml/min/cm³ (centrum
semiovale) to 1.163 ± 0.270 ml/min/cm³ (Heschl’s gyrus)
and the k2 estimates ranged from 0.040 ± 0.010 (amygdala)
to 0.112 ± 0.024 (pons).Conclusion: The parent fraction of
radioactivity at 60 min after radiotracer injection was
slightly higher compared to HPLC-based results [2].
Estimated VT values were similar to those reported
previously [2], whereas K1 and k2 values were higher. Our
preliminary data suggest that IDIF with bilateral VOI over
the internal carotid artery in combination with TLC-based
blood analysis may be an alternative to arterial input
functions for quantification of synaptic density using
[18F]SynVesT-1 PET in human brains.References:[1] He X. et
al. (2020), `Image-derived input functions for
quantification of A1 adenosine receptors availability in
mice brains using PET and [18F]CPFPX´, Frontiers in
Physiology, vol. 29, no. 10, pp. 1617.[2] Naganawa M. et al.
(2021), `First-in-human evaluation of (18)F-SynVesT-1, a
novel radioligand for PET imaging of synaptic vesicle
protein 2A´, Journal of Nuclear Medicine, vol. 62, no. 4,
pp. 561-567.},
month = {Jul},
date = {2023-07-22},
organization = {The 29th Annual Meeting of the
Organization for Human Brain Mapping,
Montréal (Canada), 22 Jul 2023 - 26
Jul 2023},
subtyp = {After Call},
cin = {INM-2 / INM-5},
cid = {I:(DE-Juel1)INM-2-20090406 / I:(DE-Juel1)INM-5-20090406},
pnm = {5253 - Neuroimaging (POF4-525) / 5252 - Brain Dysfunction
and Plasticity (POF4-525) / SleepLess - Darstellung
synaptischer Plastizität während therapeutischen
Schlafentzugs in Depression (01EW1808)},
pid = {G:(DE-HGF)POF4-5253 / G:(DE-HGF)POF4-5252 /
G:(BMBF)01EW1808},
typ = {PUB:(DE-HGF)24},
url = {https://juser.fz-juelich.de/record/1009675},
}