Radiolabeled Monocyte Chemotactic Protein 1 for the detection of inflammation in experimental atherosclerosis.
Chemotactic peptides, such as Monocyte Chemotactic Protein 1 (MCP-1), play a key role in transendothelial migration of mononuclear cells during the development and progression of atherosclerotic disease. Because atherosclerotic plaques that are precursors of acute coronary events harbor abundant macrophage infiltration, we hypothesized that the detection of a high concentration of MCP-1 receptors on inflammatory cells should noninvasively identify vulnerable plaques.


METHODS
Atherosclerotic lesions were induced by balloon deendothelialization of the abdominal aorta, which was followed by a 0.5% cholesterol diet for 16 wk in 7 New Zealand White rabbits; 5 unmanipulated rabbits, fed normal chow for 16 wk, were used as controls. Radionuclide imaging was performed immediately after intravenous (99m)Tc-labeled MCP-1 administration and 3 h later. At the end of imaging session, aortas were explanted and submitted for estimation of quantitative MCP-1 uptake (in percentage injected dose per gram, %ID/g) and pathologic characterization.


RESULTS
Atherosclerotic lesions were clearly visible in all hyperlipidemic animal gamma-imaging. No tracer uptake was seen in the control rabbits. The mean quantitative MCP-1 uptake in atherosclerotic lesions was 4-fold higher than that of the aortic specimens from the control rabbits (0.065 +/- 0.005 vs. 0.016 +/- 0.006; P < 0.0001). Histology confirmed a strong correlation between MCP-1 uptake and the number of macrophages in American Heart Association type II-IV lesions (r = 0.87, P < 0.0001).


CONCLUSIONS
Noninvasive radionuclide imaging of inflammation is feasible by MCP-1 in experimentally induced atherosclerosis. It is proposed that detection of the extent of inflammation in advanced atherosclerotic plaques may allow identification of unstable plaques.
Hartung
Dagmar
D
University of California School of Medicine, Irvine, CA 92697, USA.
Petrov
Artiom
A
Haider
Nezam
N
Fujimoto
Shinichiro
S
Blankenberg
Francis
F
Fujimoto
Ai
A
Virmani
Renu
R
Kolodgie
Frank D
FD
Strauss
H William
HW
Narula
Jagat
J
D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism*; D004036:Diet, Atherogenic; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D013670:Sodium Pertechnetate Tc 99m
D018932:Chemokine CCL2; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D013670:Sodium Pertechnetate Tc 99m