Xinlin Yang1, Anthony J Ignozzi1, Rui He1, Di Zhu1, Xisha Wang2, Mahendra D Chordia2, Dongfeng Pan2, Quanjun Cui3. 1. Department of Orthopaedic Surgery, University of Virginia School of Medicine, 400 Ray C. Hunt Drive, Suite 330, Charlottesville, VA, 22903, USA. 2. Department of Radiology, University of Virginia, Charlottesville, VA, USA. 3. Department of Orthopaedic Surgery, University of Virginia School of Medicine, 400 Ray C. Hunt Drive, Suite 330, Charlottesville, VA, 22903, USA. qc4q@virginia.edu.
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.
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.