The Synthesis and Initial Evaluation of MerTK Targeted PET Agents

Li Wang; Yubai Zhou; Xuedan Wu; Xinrui Ma; Bing Li; Ransheng Ding; Michael A. Stashko; Zhanhong Wu; Xiaodong Wang; Zibo Li

doi:10.3390/molecules27051460

Molecules (Feb 2022)

The Synthesis and Initial Evaluation of MerTK Targeted PET Agents

Li Wang,
Yubai Zhou,
Xuedan Wu,
Xinrui Ma,
Bing Li,
Ransheng Ding,
Michael A. Stashko,
Zhanhong Wu,
Xiaodong Wang,
Zibo Li

Affiliations

Li Wang: Biomedical Research Imaging Center, Department of Radiology, and UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Yubai Zhou: Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Xuedan Wu: Biomedical Research Imaging Center, Department of Radiology, and UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Xinrui Ma: Biomedical Research Imaging Center, Department of Radiology, and UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Bing Li: Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Ransheng Ding: Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Michael A. Stashko: Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Zhanhong Wu: Biomedical Research Imaging Center, Department of Radiology, and UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
Xiaodong Wang: Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Zibo Li: Biomedical Research Imaging Center, Department of Radiology, and UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA

DOI: https://doi.org/10.3390/molecules27051460
Journal volume & issue: Vol. 27, no. 5
p. 1460

Abstract

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MerTK (Mer tyrosine kinase), a receptor tyrosine kinase, is ectopically or aberrantly expressed in numerous human hematologic and solid malignancies. Although a variety of MerTK targeting therapies are being developed to enhance outcomes for patients with various cancers, the sensitivity of tumors to MerTK suppression may not be uniform due to the heterogeneity of solid tumors and different tumor stages. In this report, we develop a series of radiolabeled agents as potential MerTK PET (positron emission tomography) agents. In our initial in vivo evaluation, [18F]-MerTK-6 showed prominent uptake rate (4.79 ± 0.24%ID/g) in B16F10 tumor-bearing mice. The tumor to muscle ratio reached 1.86 and 3.09 at 0.5 and 2 h post-injection, respectively. In summary, [18F]-MerTK-6 is a promising PET agent for MerTK imaging and is worth further evaluation in future studies.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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