TY - JOUR
T1 - Development of 18F-Labeled PET Tracer Candidates for Imaging of the Abelson Non-receptor Tyrosine Kinase in Parkinson’s Disease
AU - Stéen, E. Johanna L.
AU - Park, A Yeong
AU - Beaino, Wissam
AU - Gadhe, Changdev Gorakshnath
AU - Kooijman, Esther
AU - Schuit, Robert C.
AU - Schreurs, Maxime
AU - Leferink, Prisca
AU - Hoozemans, Jeroen J. M.
AU - Kim, Jae Eun
AU - Lee, Jinhwa
AU - Windhorst, Albert D.
N1 - Funding Information: Hwajung Nam, Hyeongjun Kim, and Inyong Bae of 1ST Biotherapeutics Inc. are acknowledged for their initial contributions to this project. Publisher Copyright: © 2023 American Chemical Society.
PY - 2023/9/28
Y1 - 2023/9/28
N2 - Activated Abelson non-receptor tyrosine kinase (c-Abl) plays a harmful role in neurodegenerative conditions such as Parkinson’s disease (PD). Inhibition of c-Abl is reported to have a neuroprotective effect and be a promising therapeutic strategy for PD. We have previously identified a series of benzo[d]thiazole derivatives as selective c-Abl inhibitors from which one compound showed high therapeutic potential. Herein, we report the development of a complementary positron emission tomography (PET) tracer. In total, three PET tracer candidates were developed and eventually radiolabeled with fluorine-18 for in vivo evaluation studies in mice. Candidate [18F]3 was identified as the most promising compound, since it showed sufficient brain uptake, good washout kinetics, and satisfactory metabolic stability. In conclusion, we believe this tracer provides a good starting point to further validate and explore c-Abl as a target for therapeutic strategies against PD supported by PET.
AB - Activated Abelson non-receptor tyrosine kinase (c-Abl) plays a harmful role in neurodegenerative conditions such as Parkinson’s disease (PD). Inhibition of c-Abl is reported to have a neuroprotective effect and be a promising therapeutic strategy for PD. We have previously identified a series of benzo[d]thiazole derivatives as selective c-Abl inhibitors from which one compound showed high therapeutic potential. Herein, we report the development of a complementary positron emission tomography (PET) tracer. In total, three PET tracer candidates were developed and eventually radiolabeled with fluorine-18 for in vivo evaluation studies in mice. Candidate [18F]3 was identified as the most promising compound, since it showed sufficient brain uptake, good washout kinetics, and satisfactory metabolic stability. In conclusion, we believe this tracer provides a good starting point to further validate and explore c-Abl as a target for therapeutic strategies against PD supported by PET.
UR - http://www.scopus.com/inward/record.url?scp=85174305020&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.3c00902
DO - 10.1021/acs.jmedchem.3c00902
M3 - Article
C2 - 37712438
SN - 0022-2623
VL - 66
SP - 12990
EP - 13006
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 18
ER -