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PET Imaging of T Cells: Target Identification and Feasibility Assessment
Author(s) -
Auberson Yves P.,
Briard Emmanuelle,
Rudolph Bettina,
Kaupmann Klemens,
Smith Paul,
Oberhauser Berndt
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800241
Subject(s) - positron emission tomography , protein kinase c , tyrosine kinase , ex vivo , cancer research , in vivo , chemistry , kinase , medicine , microbiology and biotechnology , biology , in vitro , biochemistry , signal transduction , nuclear medicine
Imaging T 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 T cells, and for which lead molecules were available: protein kinase C isozyme θ (PKC θ), lymphocyte‐specific protein tyrosine kinase (Lck), zeta‐chain‐associated protein kinase 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 T cells: (5a R )‐5,5‐difluoro‐5a‐methyl‐ N ‐(1‐(( S )‐3‐(methylsulfonyl)phenyl)(tetrahydro‐2 H ‐pyran‐4‐yl)methyl)‐1 H ‐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 T cells in patients.