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 (US)
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

ASJC Scopus subject areas

Surgery
Pulmonary and Respiratory Medicine
Cardiology and Cardiovascular Medicine
Transplantation

Access to Document

10.1016/S1053-2498(02)00421-7

Cite this

@article{1a75d8978e8745bda9e530bc784db368,

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 (US)",

volume = "21",

pages = "1009--1015",

journal = "Journal of Heart and Lung Transplantation",

issn = "1053-2498",

publisher = "Elsevier USA",

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 - http://www.scopus.com/inward/record.url?scp=0036754815&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036754815&partnerID=8YFLogxK

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this