The use of 99mtechnetium-labeled MCP-1 to assess graft coronary artery disease in rat cardiac allografts

Murray H. Kown, Christina L. Jahncke, Maarten A. Lijkwan, Mark L. Koransky, Carina Mari, Gerald J. Berry, Francis G. Blankenberg, H. William Strauss, Robert C. Robbins

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1009-1015
Number of pages7
JournalJournal of Heart and Lung Transplantation
Issue number9
StatePublished - Sep 2002
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation


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