Development of contrast agents targeted to macrophage scavenger receptors for MRI of vascular inflammation.
Atherosclerosis is a leading cause of death in the U.S. Because there is a potential to prevent coronary and arterial disease through early diagnosis, there is a need for methods to image arteries in the subclinical stage as well as clinical stage using various noninvasive techniques, including magnetic resonance imaging (MRI). We describe a development of a novel MRI contrast agent targeted to plaques that will allow imaging of lesion formation. The contrast agent is directed to macrophages, one of the earliest components of developing plaques. Macrophages are labeled through the macrophage scavenger receptor A, a macrophage specific cell surface protein, using an MRI contrast agent derived from scavenger receptor ligands. We have synthesized and characterized these contrast agents with a range of relaxivities. In vitro studies show that the targeted contrast agent accumulates in macrophages, and solution studies indicate that micromolar concentrations are sufficient to produce contrast in an MR image. Cell toxicity and initial biodistribution studies indicate low toxicity, no detectable retention in normal blood vessels, and rapid clearance from blood. The promising performance of this contrast agent targeted toward vascular inflammation opens doors to tracking of other inflammatory diseases such as tumor immunotherapy and transplant acceptance using MRI.
Gustafsson
Björn
B
Department of Biomedical Engineering, University of California, Davis, California 95616, USA.
Youens
Susan
S
Louie
Angelique Y
AY
D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D002417:Cattle; D002460:Cell Line; D002746:Chlorpromazine / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051381:Rats; D051116:Receptors, Scavenger / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism
D003287:Contrast Media; D051116:Receptors, Scavenger; D012710:Serum Albumin, Bovine; D002746:Chlorpromazine