title: PET imaging detection of macrophages with a formyl peptide receptor antagonist.
abstract: Macrophages are a major inflammatory cell type involved in the development and progression of many important chronic inflammatory diseases. We previously found that apolipoprotein E-deficient (Apoe(-/-)) mice with the C57BL/6 (B6) background develop type 2 diabetes mellitus (T2DM) and accelerated atherosclerosis when fed a Western diet and that there are increased macrophage infiltrations in pancreatic islets and aorta. The formyl peptide receptor 1 (FPR1) is abundantly expressed on the surface of macrophages. The purpose of this study was to evaluate the applicability of cinnamoyl-F-(D)L-F-(D)L-F (cFLFLF), a natural FPR1 antagonist, to detection of macrophages in the pancreatic islets and aorta. (64)Cu labeled cFLFLF and (18)F-fluorodeoxyglucose (FDG) were administered to mice with or without T2DM. Diabetic mice showed an increased (18)FDG uptake in the subcutaneous fat compared with control mice, but pancreatic uptake was minimal for either group. In contrast, diabetic mice exhibited visually noticeable more cFLFLF-(64)Cu retention in pancreas and liver than control mice. The heart and pancreas isolated from diabetic mice contained more macrophages and showed stronger PET signals than those of control mice. Flow cytometry analysis revealed the presence of macrophages but not neutrophils in pancreatic islets. Real-time PCR analysis revealed much higher FPR1 expression in pancreatic islets of diabetic over control mice. Autoradiography and immunohistochemical analysis confirmed abundant FPR1 expression in atherosclerotic lesions. Thus, (64)Cu-labeled cFLFLF peptide is a more effective PET agent for detecting macrophages compared to FDG.
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA 22908.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA 22908.
authors.forename: Bijoy
authors.initials: B
authors.lastname: Kundu
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA 22908.
authors.forename: Min
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA 22908.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA 22908.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA 22908.
authors.forename: Mahendra D
authors.initials: MD
authors.lastname: Chordia
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA 22908.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA 22908.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Pan
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA 22908.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA 22908. Electronic address: ws4v@virginia.edu.
authors.forename: Weibin
authors.initials: W
authors.lastname: Shi
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging; D005260:Female; D007515:Islets of Langerhans / Q000000981:diagnostic imaging; D008264:Macrophages / Q000000981:diagnostic imaging*; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods*; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors*
chemical_list: D009842:Oligopeptides; D044042:Receptors, Formyl Peptide
keywords: Inflammation; Macrophage; PET imaging; Type 2 diabetes