title: Direct in vivo evidence of activated macrophages in human osteoarthritis.
abstract: Through binding to folate receptor-β (FR-β), the new (99m)Tc-EC20 (Etarfolatide) imaging technique detects activated but not resting macrophages in vivo. The goal of this study was to investigate macrophage-related inflammation in osteoarthritis (OA).
  
  
  
  Twenty-five individuals (50 knees) with symptomatic OA of at least one knee underwent SPECT-CT imaging of both knees and planar imaging of the whole body after injection of Etarfolatide. Scans and knee radiographs were scored blinded to clinical information including knee and other joint site pain severity. Measures of association controlled for age, gender, body mass index (BMI) and employed repeated measures to adjust for correlation between knees.
  
  
  
  Activated macrophages were present in the majority (76%) of knees. The quantity of knee-related macrophages was significantly associated with knee pain severity (R = 0.60, P < 0.0001) and radiographic knee OA severity including joint space narrowing (R = 0.68, P = 0.007), and osteophyte (R = 0.66, P = 0.001). Macrophages were also localized to joints commonly affected by OA including hand finger joints (12%), thumb bases (28%), shoulders (26%), great toes (18%) and ankles (12%). The presence of joint pain at fingers, wrists, ankles and great toes was significantly positively associated with presence of activated macrophages at these sites (P < 0.0001-0.04).
  
  
  
  This study provides the first direct in vivo evidence for macrophage involvement in OA in a substantial proportion of human knees. The association of quantity of activated macrophages with radiographic knee OA severity and joint symptoms suggests that drugs targeting macrophages and macrophage-associated inflammatory pathways may have the potential to be both symptom and structure modifying.
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA; Department of Medicine, Duke University School of Medicine, Durham, NC, USA. Electronic address: vbk@duke.edu.
authors.forename: V B
authors.initials: VB
authors.lastname: Kraus
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: G
authors.initials: G
authors.lastname: McDaniel
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Huebner
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: T V
authors.initials: TV
authors.lastname: Stabler
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Pieper
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Shipes
authors.affiliation: Department of Radiology, The Medical Physics Program and Nuclear Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Petry
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Low
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: J
authors.initials: J
authors.lastname: Shen
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: McNearney
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: P
authors.initials: P
authors.lastname: Mitchell
mesh_terms: D006801:Humans; D007719:Knee Joint; D008264:Macrophages; D020370:Osteoarthritis, Knee; D054850:Osteophyte; D011859:Radiography
keywords: Inflammation; Joint pain; Knee; Macrophage; Osteoarthritis