[11C]NCGG401, a novel PET ligand for imaging of colony stimulating factor 1 receptors

Aya Ogata; Bin Ji; Takashi Yamada; Saori Hattori; Junichiro Abe; Hiroshi Ikenuma; Masanori Ichise; Hiroko Koyama; Masaaki Suzuki; Takashi Kato; Kengo Ito; Yasuyuki Kimura

doi:10.1016/j.bmcl.2022.128704

[¹¹C]NCGG401, a novel PET ligand for imaging of colony stimulating factor 1 receptors

Bioorg Med Chem Lett. 2022 Jun 1:65:128704. doi: 10.1016/j.bmcl.2022.128704. Epub 2022 Mar 26.

Authors

Affiliations

¹ Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology (NCGG), Obu, Japan; Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science (GUMS), Kani, Japan. Electronic address: aogata@u-gifu-ms.ac.jp.
² Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology (NCGG), Obu, Japan; Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan; Department of Radiopharmacy and Molecular Imaging, School of Pharmacy, Fudan University, Shanghai, China.
³ Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology (NCGG), Obu, Japan.
⁴ Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology (NCGG), Obu, Japan; Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
⁵ Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Gifu, Japan.
⁶ Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology (NCGG), Obu, Japan; Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan. Electronic address: yazkim@ncgg.go.jp.

PMID: 35351586
DOI: 10.1016/j.bmcl.2022.128704

Abstract

Colony-stimulating factor 1 receptors (CSF1R) are expressed exclusively on microglia in the central nervous system. The receptors regulate immune responses by controlling the survival and activity of microglia and are intricately involved in the pathophysiology of Alzheimer's disease. In this study, we developed [¹¹C]NCGG401, a positron emission tomography (PET) ligand, targeting for CSF1R as an imaging biomarker for microglial pathophysiology in Alzheimer's disease. NCGG401 showed a high potency to inhibit human CSF1R kinase activity and a high binding affinity to human CSF1R. PET imaging with [¹¹C]NCGG401 in healthy rats showed a good brain permeability. Furthermore, the specific binding component was determined by postmortem autoradiography in rat brain and human hippocampal sections. The knowledge of the characteristics of [¹¹C]NCCC401, our initial CSF1R compound, we have obtained may be useful for further development and optimization of CSF1R radioligands for PET imaging of microglia.

Keywords: Alzheimer’s disease; Colony-stimulating factor 1 receptor; Microglia; Positron emission tomography.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / metabolism
Animals
Brain / diagnostic imaging
Brain / metabolism
Disease Models, Animal
Ligands
Macrophage Colony-Stimulating Factor* / metabolism
Microglia / metabolism
Positron-Emission Tomography / methods
Rats
Receptor, Macrophage Colony-Stimulating Factor / metabolism
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor

Substances

Ligands
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
Macrophage Colony-Stimulating Factor
Receptor, Macrophage Colony-Stimulating Factor