title: Targeting formyl peptide receptor 1 of activated macrophages to monitor inflammation of experimental osteoarthritis in rat.
abstract: Macrophages play a crucial role in the pathogenesis of osteoarthritis (OA). In this study, the feasibility of a formyl peptide receptor 1 (Fpr1)-targeting peptide probe cFLFLF-PEG-(64) Cu via positron emission tomography (PET) imaging was investigated for detection of macrophage activity during development of OA. Monoiodoacetate (MIA) was intraarticularly injected into the knee joint of Sprague-Dawley rats to induce OA. Five days later, cFLFLF-PEG-(64) Cu (∼7,400 kBq/rat) was injected into the tail vein and microPET/CT imaging was performed to assess the OA inflammation by detecting infiltration of macrophages by Fpr1 expression. In addition, a murine macrophage cell line RAW264.7 and two fluorescent probes cFLFLF-PEG-cyanine 7 (cFLFLF-PEG-Cy7) and cFLFLF-PEG-cyanine 5 (cFLFLF-PEG-Cy5) were used to define the binding specificity of the peptide to macrophages. It was found with the MIA model that the maximal standard uptake values (SUVmax ) for right (MIA treated) and left (control) knees were 17.96 ± 5.45 and 3.00 ± 1.40, respectively. Histological evaluation of cryomicrotome sections showed that Fpr1 expression, cFLFLF-PEG-Cy5 binding, and tartrate-resistant acid phosphatase activity were elevated in the injured synovial membranes. The in vitro experiments demonstrated that both fluorescent peptide probes could bind specifically to RAW264.7 cells, which was blocked by cFLFLF but not by the scramble peptide. The findings highlighted the use of cFLFLF-PEG-(64) Cu/PET as an effective method potentially applied for detection and treatment evaluation of OA. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1529-1538, 2016.
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia, Charlottesville, Virginia, 22903.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia, 22903.
authors.forename: Mahendra D
authors.initials: MD
authors.lastname: Chordia
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia, Charlottesville, Virginia, 22903.|Department of Orthopaedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, PR China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia, Charlottesville, Virginia, 22903.
authors.forename: John L
authors.initials: JL
authors.lastname: Graves
authors.affiliation: Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia, 22903.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia, Charlottesville, Virginia, 22903.
authors.forename: Yong-Sang
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia, Charlottesville, Virginia, 22903.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia, 22903.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Pan
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia, Charlottesville, Virginia, 22903.
authors.forename: Quanjun
authors.initials: Q
authors.lastname: Cui
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging* / Q000276:immunology; D005240:Feasibility Studies; D005260:Female; D008264:Macrophages; D009842:Oligopeptides; D009942:Organometallic Compounds; D010003:Osteoarthritis / Q000000981:diagnostic imaging* / Q000276:immunology; D011092:Polyethylene Glycols; D049268:Positron-Emission Tomography; D017207:Rats, Sprague-Dawley; D044042:Receptors, Formyl Peptide / Q000032:analysis*
chemical_list: D009842:Oligopeptides; D009942:Organometallic Compounds; D044042:Receptors, Formyl Peptide; C542078:cFLFLFK-PEG-64Cu; D011092:Polyethylene Glycols
keywords: cFLFLF peptide; formyl peptide receptor 1; macrophages; osteoarthritis; positron emission tomography