RT Journal Article
SR Electronic
T1 Radiolabeled Monocyte Chemotactic Protein 1 for the Detection of Inflammation in Experimental Atherosclerosis
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1816
OP 1821
DO 10.2967/jnumed.107.043463
VO 48
IS 11
A1 Dagmar Hartung
A1 Artiom Petrov
A1 Nezam Haider
A1 Shinichiro Fujimoto
A1 Francis Blankenberg
A1 Ai Fujimoto
A1 Renu Virmani
A1 Frank D. Kolodgie
A1 H. William Strauss
A1 Jagat Narula
YR 2007
UL http://jnm.snmjournals.org/content/48/11/1816.abstract
AB 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 99mTc-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 γ-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). Conclusion: 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.