2022 Fiscal Year Annual Research Report
Neutrophil-Specific PET Cellular Imaging for ARDS
| Project/Area Number |
22H03027
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| Allocation Type | Single-year Grants |
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| Research Institution | Okayama University |
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Principal Investigator |
樋口 隆弘 岡山大学, 医歯薬学域, 教授 (30739850)
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| Project Period (FY) |
2022-04-01 – 2026-03-31
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| Keywords | ARDS / PET / CXCR2 / COVID-19 / neutrophil |
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| Outline of Annual Research Achievements |
The goal of this study is to develop a PET imaging assay that can specifically detect neutrophils of the lung and other organs by targeting the CXCR2, a
chemokine receptor specifically expressed on neutrophils.
At present, there is no in vivo imaging technique that can specifically visualize local neutrophil infiltration identified via systemic scanning of human body as well as animals. Therefore, we aim to achieve this by using cutting edge PET molecular imaging technology, which can visualize biomarker molecules with high sensitivity.
Considering future clinical applications, to develop of small molecule tracers for F18-labeling that are easy to handle in clinical settings, we designed and synthesized PET tracer candidates targeting CXCR2 in this year. To evaluate the affinity of these radiotracers, cold references, i.e. their non-radioactive references, were synthesized first. The direct radiofluorination without the special preparation of tosylate precursor was also methodology investigation to facilitate the radiolabelling protocol from original structures. In contract, the cold references of urea series of compounds and the corresponding precursors for radiolabelling were also synthesized.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We designed and synthesized PET tracer candidates targeting CXCR2. To evaluate the affinity of these radiotracers, cold references, i.e. their non-radioactive references, were synthesized first. The direct radiofluorination without the special preparation of tosylate precursor was also methodology investigation to facilitate the radiolabelling protocol from original structures.
The advantage of using reparixin with direct fluorination is that commercially available one could be used directly to test the labelling protocol. In contract, the cold references of urea series of compounds and the corresponding precursors for radiolabelling were also synthesized.
Since the initial first-year experimental plan has been completed, we believe that the research progress is generally on track.
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| Strategy for Future Research Activity |
In this project, we will develop neutrophil-specific PET imaging of inflammation by 1) targeting CXCR2, a chemokine receptor specifically expressed on neutrophils, 2) using molecular imaging with PET imaging technology that enables highly sensitive molecular detection, 3) designing an 18F-labeled small molecule tracer formulation suitable for clinical application, through evaluation in synthetic, cellular, and animal experiments.
For accomplished this project, we’ll do in vitro assays to test the binding affinity, selectivity, and stability of the compounds. And then, we’ll stablish and optimize radiolabelling methods of the PET tracers. Next step, ex vivo analysis and biodistribution will be done: in vivo evaluation of at least one candidate tracer in a healthy rodent. Finally, we’ll do the longitudinal PET imaging using the rodent animal models of this disease.
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[Journal Article] Imaging of C-X-C Motif Chemokine Receptor 4 Expression in 690 Patients with Solid or Hematologic Neoplasms using 68Ga-PentixaFor PET2022
Author(s)
Buck AK, Haug A, Dreher N, Lambertini A, Higuchi T, Lapa C, Weich A, Pomper MG, Wester HJ, Zehndner A, Schirbel A, Samnick S, Hacker M, Pichler V, Hahner S, Fassnacht M, Einsele H, Serfling SE, Werner RA.
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Journal Title
Journal of Nuclear Medicine
Volume: 63
Pages: 1687-1692
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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