JNM: Preclinical imaging of atherosclerosis, vulnerable plaque shows promise

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The imaging modalities to acquire information on both anatomy and pathobiology in the same imaging session using either hybrid technology (nuclear combined with CT) or MRI combined with novel probes for preclinical imaging of atherosclerosis and vulnerable plaque have been discussed in an article published in the May 2010 supplement of the Journal of Nuclear Medicine.

Advances in molecular biology, development of genetically altered mice, and careful observation of human pathologic specimens have produced a picture of the biologic and anatomic initiation and progression of atherosclerosis.

“This complex picture presents targets for the development of probes that, coupled with rapid advances in technology for both small-animal and clinical hybrid SPECT, PET and MRI platforms, has broadened capabilities for both preclinical research and clinical imaging,” according to Mehran M. Sadeghi, MD, associate professor of medicine at Yale University School of Medicine, New Haven, Connecticut and colleagues.

Inflammation is an important component of atherosclerosis. 18F-FDG is widely available for tumor imaging and shows promise as a marker of inflammatory activity of atherosclerotic plaque and plaque burden. It is being tested as a surrogate endpoint in drug trials, noted the authors.

Experimental studies have also shown that a single photon-labeled probe that binds the lectin like oxidized-1 low-density lipoprotein (LDL) receptor is taken up in atherosclerotic lesions and shows promise as an agent for imaging inflammation in atherosclerosis.

Radiolabeled metalloproteinase inhibitors (MPIs) that target both inflammation and remodeling show promise in preclinical experiments. MRI alone offers information on anatomy and plaque composition and can be combined with imaging probes that target biologic processes.

Nanoparticles with paramagnetic properties have been designed to target angiogenesis. Iron-based particles, are taken up by macrophages in atheroma, and ultrasuperparamagnetic iron oxide-MRI has the potential to become an approach to image inflamed and active atherosclerotic plaques with further refinements in acquisition parameters, according to Sadeghi and colleagues.

All of these approaches show promise for imaging many of the known manifestations of atherosclerotic plaque instability, but application in the clinic will require the availability of nontoxic low-molecular-weight probes, imaging platforms, and demonstration of cost-effectiveness, the authors concluded.