PET Imaging of T Cells: Target Identification and Feasibility Assessment.
ChemMedChem
; 13(15): 1566-1579, 2018 08 10.
Article
em En
| MEDLINE
| ID: mdl-29856125
ABSTRACT
Imaging Tâ
cells using positron emission tomography (PET) would be highly useful for diagnosis and monitoring in immunology and oncology patients. There are, however, no obvious targets that can be used to develop imaging agents for this purpose. We evaluated several potential target proteins with selective expression in Tâ
cells, and for which lead molecules were available protein kinaseâ
C isozymeâ
θ (PKCâ
θ), lymphocyte-specific protein tyrosine kinase (Lck), zeta-chain-associated protein kinaseâ
70 (ZAP70), and interleukin-2-inducible T-cell kinase (Itk). Ultimately, we focused on Itk and identified a tool molecule with properties suitable for in vivo imaging of Tâ
cells (5aR)-5,5-difluoro-5a-methyl-N-(1-((S)-3-(methylsulfonyl)phenyl)(tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)-1,4,4a,5,5a,6-hexahydrocyclopropa[f]indazole-3-carboxamide (23). Although it does not have the optimal profile for clinical use, this molecule indicates that it might be possible to develop Itk-selective PET ligands for imaging the distribution of Tâ
cells in patients.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Tomografia por Emissão de Pósitrons
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
ChemMedChem
Assunto da revista:
FARMACOLOGIA
/
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Suíça