The use of (99m)technetium-labeled MCP-1 to assess graft coronary artery disease in rat cardiac allografts.
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.
Kown
Murray H
MH
Department of Cardiothoracic Surgery, Stanford University School of Medicine, California 94305, USA.
Jahncke
Christina L
CL
Lijkwan
Maarten A
MA
Koransky
Mark L
ML
Mari
Carina
C
Berry
Gerald J
GJ
Blankenberg
Francis G
FG
Strauss
H William
HW
Robbins
Robert C
RC
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
D018932:Chemokine CCL2; D019275:Radiopharmaceuticals; D013667:Technetium