Abstract
Purpose
Although inflammation has been recognized as a key process in the pathogenesis of osteoarthritis (OA), there remains no clinical noninvasive imaging modality that can specifically diagnose inflammatory activity of OA. In this study, a formyl peptide receptor 1 (Fpr1) targeting probe cFLFLF-PEG-HYNIC-99mTc and single-photon emission computed tomography (SPECT) imaging was used to detect inflammatory activity by targeting macrophages involved in the pathogenesis of OA.
Procedures
In vitro experiments were performed to evaluate Fpr1 expression during macrophage inflammatory response. In the in vivo studies, anterior cruciate ligament transection (ACLT) surgery was performed, and magnetic resonance imaging (MRI) and histological data were assessed to analyze the OA model in both mice and rats. The radioactive probe cFLFLF-PEG-HYNIC-99mTc and SPECT imaging were used to corroborate OA-related inflammation and compare ACLT vs sham knees.
Results
In vitro macrophage activation resulted in a remarkable increase in Fpr1 expression. In vivo experiments in mice and rats produced similar results. MRI and histological analysis demonstrated significant joint degeneration in the ACLT knee. The ACLT knee produced a much stronger signal from the probe when compared to the sham knee. It is important to note that the ratio of ACLT/sham knee signal intensity decreased with OA progression, indicating greater differences earlier in the progression of OA.
Conclusion
The radioactive probe cFLFLF-PEG-HYNIC-99mTc and SPECT imaging are effective for detecting and monitoring inflammation during OA progression by targeting Fpr1 expression in the knee joint.
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Funding
The work supported by the NIH/NIAMS grant No. 5R21AR070987 and the Seed Grant Program sponsored by University of Virginia Center for Engineering in Medicine No. LC00182.
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XY: Research design, acquisition and analysis of data, drafting, and revising the paper. AJI: Data acquisition, drafting, and revising the paper. RH, DZ, and XW: Acquisition and analysis of data. MC and DP: Acquisition and analysis of data and revising the paper. QC: Research design, analysis of data, and revising the paper.
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Yang, X., Ignozzi, A.J., He, R. et al. Detection of Osteoarthritis Inflammation by Single-Photon Emission Computed Tomography Based on an Inflammation-Targeting Peptide cFLFLF. Mol Imaging Biol 23, 895–904 (2021). https://doi.org/10.1007/s11307-021-01616-x
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DOI: https://doi.org/10.1007/s11307-021-01616-x