Development and Initial Characterization of the First 18F-CXCR2-Targeting Radiotracer for PET Imaging of Neutrophils
Spatz P, Chen X, Reichau K, Huber M, Mühlig S, Matsusaka Y, Schiedel M, Higuchi T, Decker M (2024)
Publication Type: Journal article
Publication year: 2024
Journal
Book Volume: 67
Pages Range: 6327-6343
Journal Issue: 8
DOI: 10.1021/acs.jmedchem.3c02285
Abstract
The interleukin-8 receptor beta (CXCR2) is a highly promising target for molecular imaging of inflammation and inflammatory diseases. This is due to its almost exclusive expression on neutrophils. Modified fluorinated ligands were designed based on a squaramide template, with different modification sites and synthetic strategies explored. Promising candidates were then tested for affinity to CXCR2 in a NanoBRET competition assay, resulting in tracer candidate 16b. As direct 18F-labeling using established tosyl chemistry did not yield the expected radiotracer, an indirect labeling approach was developed. The radiotracer [18F]16b was obtained with a radiochemical yield of 15% using tert-butyl (S)-3-(tosyloxy)pyrrolidine carboxylate and a pentafluorophenol ester. The subsequent time-dependent uptake of [18F]16b in CXCR2-negative and CXCR2-overexpressing human embryonic kidney cells confirmed the radiotracer’s specificity. Further studies with human neutrophils revealed its diagnostic potential for functional imaging of neutrophils.
Authors with CRIS profile
Max Huber
Lehrstuhl für Pharmazeutische Chemie
Matthias Schiedel
Lehrstuhl für Pharmazeutische Chemie
Involved external institutions
Julius-Maximilians-Universität Würzburg
Germany (DE)
Universität Augsburg
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
Germany (DE)
Universität Augsburg
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
How to cite
APA:
Spatz, P., Chen, X., Reichau, K., Huber, M., Mühlig, S., Matsusaka, Y.,... Decker, M. (2024). Development and Initial Characterization of the First 18F-CXCR2-Targeting Radiotracer for PET Imaging of Neutrophils. Journal of Medicinal Chemistry, 67(8), 6327-6343. https://doi.org/10.1021/acs.jmedchem.3c02285
MLA:
Spatz, Philipp, et al. "Development and Initial Characterization of the First 18F-CXCR2-Targeting Radiotracer for PET Imaging of Neutrophils." Journal of Medicinal Chemistry 67.8 (2024): 6327-6343.
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