Development of [18F]MIPS15692, a radiotracer with in vitro proof-of-concept for the imaging of MER tyrosine kinase (MERTK) in neuroinflammatory disease

SW Wong; L Vivash; R Mudududdla; N Nguyen; SJ Hermans; DM Shackleford; J Field; L Xue; A Aprico; NC Hancock; M Haskali; MA Stashko; SV Frye; X Wang; MD Binder; U Ackermann; MW Parker; TJ Kilpatrick; JB Baell

Journal article

Development of [18F]MIPS15692, a radiotracer with in vitro proof-of-concept for the imaging of MER tyrosine kinase (MERTK) in neuroinflammatory disease

SW Wong, L Vivash, R Mudududdla, N Nguyen, SJ Hermans, DM Shackleford, J Field, L Xue, A Aprico, NC Hancock, M Haskali, MA Stashko, SV Frye, X Wang, MD Binder, U Ackermann, MW Parker, TJ Kilpatrick, JB Baell

European Journal of Medicinal Chemistry | Published : 2021

DOI: 10.1016/j.ejmech.2021.113822

Abstract

MER tyrosine kinase (MERTK) upregulation is associated with M2 polarization of microglia, which plays a vital role in neuroregeneration following damage induced by neuroinflammatory diseases such as multiple sclerosis (MS). Therefore, a radiotracer specific for MERTK could be of great utility in the clinical management of MS, for the detection and differentiation of neuroregenerative and neurodegenerative processes. This study aimed to develop an [18F] ligand with high affinity and selectivity for MERTK as a potential positron emission tomography (PET) radiotracer. MIPS15691 and MIPS15692 were synthesized and kinase assays were utilized to determine potency and selectivity for MERTK. Both co..

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University of Melbourne Researchers

Judith Field Author

Andrea Aprico Author

Mo Haskali Author

Michele Binder Author

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Grants

Awarded by Biogen

Funding Acknowledgements

The National Health and Medical Research Council of Australia (NHMRC) is thanked for research support for J.B.B. (2017-2021 Principal Research Fellowship #1117602 and Project Grant #1142814), for T.J.K (2020-2024 NHMRC Investigator grant ##1175775). and for M.W.P. (2017-2021 Senior Principal Research Fellowship #1117183; 2021-2025 Investigator grant #1194263). The Perpetual Trustees Company Ltd is also thanked for providing research support for this project. The study was also funded by the Melbourne Neuroscience Institute Interdisciplinary Seed Grant. The Australian Institute of Nuclear Science and Engineering (AINSE Ltd.) is thanked for financial support for S.W.W. through the Postgraduate Research Award.