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 (99mTc)-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 99mTc-MCP-1 and killed after 1 hour. Radioactivity of heart tissues was measured and standardized to uptake in the overall blood pool. Two-dimensional 99mTc-MCP-1 uptake (autoradiographs) was imaged by exposing 50-μm 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 99mTc-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 (R2 = 0.50). No significant differences were seen in acute rejection scores. Conclusion: 99mTc-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.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine