Longitudinal preclinical evaluation of the novel radioligand [11C]CHDI-626 for PET imaging of mutant huntingtin aggregates in Huntington's disease.
Animal model
Biomarker
HD
Neuroimaging
mHTT
Journal
European journal of nuclear medicine and molecular imaging
ISSN: 1619-7089
Titre abrégé: Eur J Nucl Med Mol Imaging
Pays: Germany
ID NLM: 101140988
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
24
08
2021
accepted:
28
09
2021
pubmed:
16
10
2021
medline:
27
4
2022
entrez:
15
10
2021
Statut:
ppublish
Résumé
As several therapies aimed at lowering mutant huntingtin (mHTT) brain levels in Huntington's disease (HD) are currently being investigated, noninvasive positron emission tomography (PET) imaging of mHTT could be utilized to directly evaluate therapeutic efficacy and monitor disease progression. Here we characterized and longitudinally assessed the novel radioligand [ After evaluating radiometabolites and radioligand kinetics, we conducted longitudinal dynamic PET imaging at 3, 6, 9, and 13 months of age (M) in wild-type (WT, n = 17) and heterozygous (HET, n = 23) zQ175DN mice. Statistical analysis was performed to evaluate temporal and genotypic differences. Cross-sectional cohorts at each longitudinal time point were included for post-mortem [ Despite fast metabolism and kinetics, the radioligand was suitable for PET imaging of mHTT. Longitudinal quantification could discriminate between genotypes already at premanifest stage (3 M), showing an age-associated increase in signal in HET mice in parallel with mHTT aggregate load progression, as supported by the post-mortem [ With clinical evaluation underway, [
Identifiants
pubmed: 34651228
doi: 10.1007/s00259-021-05578-8
pii: 10.1007/s00259-021-05578-8
pmc: PMC8921134
doi:
Substances chimiques
Carbon Radioisotopes
0
Carbon-11
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1166-1175Informations de copyright
© 2021. The Author(s).
Références
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