PMID- 12231372 OWN - NLM STAT- MEDLINE DCOM- 20021218 LR - 20190922 IS - 1053-2498 (Print) IS - 1053-2498 (Linking) VI - 21 IP - 9 DP - 2002 Sep TI - The use of (99m)technetium-labeled MCP-1 to assess graft coronary artery disease in rat cardiac allografts. PG - 1009-15 AB - 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. CONCLUSION: (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. FAU - Kown, Murray H AU - Kown MH AD - Department of Cardiothoracic Surgery, Stanford University School of Medicine, California 94305, USA. FAU - Jahncke, Christina L AU - Jahncke CL FAU - Lijkwan, Maarten A AU - Lijkwan MA FAU - Koransky, Mark L AU - Koransky ML FAU - Mari, Carina AU - Mari C FAU - Berry, Gerald J AU - Berry GJ FAU - Blankenberg, Francis G AU - Blankenberg FG FAU - Strauss, H William AU - Strauss HW FAU - Robbins, Robert C AU - Robbins RC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Heart Lung Transplant JT - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JID - 9102703 RN - 0 (Chemokine CCL2) RN - 0 (Radiopharmaceuticals) RN - 7440-26-8 (Technetium) SB - IM MH - Animals MH - *Chemokine CCL2/metabolism MH - Coronary Artery Disease/*immunology/metabolism/pathology MH - Graft Occlusion, Vascular/*immunology/metabolism/pathology MH - Heart Transplantation/*adverse effects MH - Image Processing, Computer-Assisted MH - Immunohistochemistry MH - Male MH - *Radiopharmaceuticals/metabolism MH - Rats MH - *Technetium EDAT- 2002/09/17 10:00 MHDA- 2002/12/19 04:00 CRDT- 2002/09/17 10:00 PHST- 2002/09/17 10:00 [pubmed] PHST- 2002/12/19 04:00 [medline] PHST- 2002/09/17 10:00 [entrez] AID - S1053249802004217 [pii] AID - 10.1016/s1053-2498(02)00421-7 [doi] PST - ppublish SO - J Heart Lung Transplant. 2002 Sep;21(9):1009-15. doi: 10.1016/s1053-2498(02)00421-7.