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

doi:10.1016/S1053-2498(02)00421-7

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 journal › Article › peer-review

6 Scopus citations

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 (^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 language	English
Pages (from-to)	1009-1015
Number of pages	7
Journal	Journal of Heart and Lung Transplantation
Volume	21
Issue number	9
DOIs	https://doi.org/10.1016/S1053-2498(02)00421-7
State	Published - Sep 2002
Externally published	Yes

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10.1016/S1053-2498(02)00421-7

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@article{2f3c3c96ac024f6abe927d0af73d3328,

title = "The use of 99mtechnetium-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 (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.",

author = "Kown, \{Murray H.\} and Jahncke, \{Christina L.\} and Lijkwan, \{Maarten A.\} and Koransky, \{Mark L.\} and Carina Mari and Berry, \{Gerald J.\} and Blankenberg, \{Francis G.\} and Strauss, \{H. William\} and Robbins, \{Robert C.\}",

note = "Funding Information: ACKNOWLEDGMENTS This work was supported by the Russian Foundation for Basic Research, project nos. 01–03–33034 and 01– 03–32723. We thank the RFBR for supporting access to the Cambridge Structural Database [2], project no. 02– 07–90322.",

year = "2002",

month = sep,

doi = "10.1016/S1053-2498(02)00421-7",

language = "English",

volume = "21",

pages = "1009--1015",

journal = "Journal of Heart and Lung Transplantation",

issn = "1053-2498",

publisher = "Elsevier Inc.",

number = "9",

}

TY - JOUR

T1 - The use of 99mtechnetium-labeled MCP-1 to assess graft coronary artery disease in rat cardiac allografts

AU - Kown, Murray H.

AU - Jahncke, Christina L.

AU - Lijkwan, Maarten A.

AU - Koransky, Mark L.

AU - Mari, Carina

AU - Berry, Gerald J.

AU - Blankenberg, Francis G.

AU - Strauss, H. William

AU - Robbins, Robert C.

N1 - Funding Information: ACKNOWLEDGMENTS This work was supported by the Russian Foundation for Basic Research, project nos. 01–03–33034 and 01– 03–32723. We thank the RFBR for supporting access to the Cambridge Structural Database [2], project no. 02– 07–90322.

PY - 2002/9

Y1 - 2002/9

N2 - 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.

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 (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.

UR - https://www.scopus.com/pages/publications/0036754815

U2 - 10.1016/S1053-2498(02)00421-7

DO - 10.1016/S1053-2498(02)00421-7

M3 - Article

C2 - 12231372

AN - SCOPUS:0036754815

SN - 1053-2498

VL - 21

SP - 1009

EP - 1015

JO - Journal of Heart and Lung Transplantation

JF - Journal of Heart and Lung Transplantation

IS - 9

ER -

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

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