title: The use of (99m)technetium-labeled MCP-1 to assess graft coronary artery disease in rat cardiac allografts.
abstract: BACKGROUND
  Monocyte chemoattractant protein-1 (MCP-1) is associated with the development of graft coronary artery disease (GCAD) following cardiac transplantation. This study assessed whether technetium 99m ((99m)Tc)-labeled MCP-1 binds its receptors in chronic cardiac transplants and thereby provides a potential modality to assess GCAD.
  
  
  METHODS
  Allogeneic (PVG-->ACI, n = 9) and syngeneic (ACI-->ACI, n = 9) rat heterotopic heart transplants were performed. Allograft recipients were treated with 7.5 mg/kg per day of Cyclosporin A for 10 days until tolerance was achieved. After 90 days, animals were injected intravenously with (99m)Tc-MCP-1 and killed after 1 hour. Radioactivity of heart tissues was measured and standardized to uptake in the overall blood pool. Two-dimensional (99m)Tc-MCP-1 uptake (autoradiographs) was imaged by exposing 50-microm sections on a phosphoimager overnight. ED-1 staining of monocyte/macrophages was performed on serial sections. Additional sections were stained with elastin von Gieson and hematoxylin. Hearts were scored for luminal narrowing and intima/media ratio (I/M) with computerized image analysis.
  
  
  RESULTS
  Allografts exhibited significantly more luminal narrowing (22.5 +/- 10.7% vs 2.6 +/- 4.6, p = 0.0005) and higher I/M (0.173 +/- 0.151 vs 0.015 +/- 0.029, p = 0.0088) than isografts. The ratio of (99m)Tc-MCP-1 uptake in allografts (1.04 +/- 0.4) was greater than that of isograft controls (0.72 +/- 0.11, p = 0.03). Pixel counts of autoradiographs and ED-1-stained sections demonstrated a modest correlation between the two (R(2) = 0.50). No significant differences were seen in acute rejection scores.
  
  
  CONCLUSIONS
  (99m)Tc-MCP-1 uptake was higher in allografts vs isografts and was consistent with a greater degree of GCAD. These data demonstrating increased radiopharmaceutical uptake in hearts with GCAD provide a foundation for the development of a potentially non-invasive imaging assay of this disease process in heart transplantation.
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University School of Medicine, California 94305, USA.
authors.forename: Murray H
authors.initials: MH
authors.lastname: Kown
authors.forename: Christina L
authors.initials: CL
authors.lastname: Jahncke
authors.forename: Maarten A
authors.initials: MA
authors.lastname: Lijkwan
authors.forename: Mark L
authors.initials: ML
authors.lastname: Koransky
authors.forename: Carina
authors.initials: C
authors.lastname: Mari
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Berry
authors.forename: Francis G
authors.initials: FG
authors.lastname: Blankenberg
authors.forename: H William
authors.initials: HW
authors.lastname: Strauss
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robbins
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D003324:Coronary Artery Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006083:Graft Occlusion, Vascular / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016027:Heart Transplantation / Q000009:adverse effects*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D019275:Radiopharmaceuticals / Q000378:metabolism; D051381:Rats; D013667:Technetium
chemical_list: D018932:Chemokine CCL2; D019275:Radiopharmaceuticals; D013667:Technetium