Development of radiocontrast agents for vascular imaging: progress to date.
The revolution in molecular imaging techniques is profoundly changing the understanding of the pathophysiology and treatment of atherosclerosis. With these rapid changes there is an increasing demand for development of sensitive and well tolerated novel imaging agents that can be rapidly translated from small animal models into patients with atherosclerosis. Nuclear medicine and positron emission tomography techniques have the ability to detect and serially monitor a variety of biologic and pathophysiologic processes usually with tracer quantities of radiolabeled peptides, drugs, and other molecules at dosages free of pharmacologic adverse effects unlike the current generation of intravenous agents required for magnetic resonance imaging (MRI) and computed axial tomography (CT) scanning. A representative sampling of the wide array of radiopharmaceuticals developed specifically for radionuclide imaging of atherosclerosis, that have been approved for clinical use and those in pre-clinical trials, have been reviewed in this article. The presence of an inflammatory stimulus increases expression of CC (cysteine-cysteine motif) chemokine receptor (CCR)-2 on monocytes and macrophages, and somatostatin receptors on T lymphocytes. Radiolabeled monocyte chemoattractant protein (MCP)-1 binds with high affinity to CCR-2 and can be used to detect subacute and chronic inflammatory lesions. Similarly, radiolabeled octreotide or depreotide can be used to detect activated T lymphocytes which may identify the vulnerable plaque. Animal models indicate that (99m)Tc-annexin V, (125)I-MCP-1 and [(18)F]-fluoro-2-deoxyglucose are effective in identifying apoptotic cell death, macrophage infiltration and metabolic activity in atheromatous lesions, respectively. Expression of alpha(v)beta(3) integrin is increased in activated endothelial cells and vascular smooth muscle cells after vascular injury, and alpha(v)beta(3) integrin is minimally expressed on smooth muscle cells and is not expressed on quiescent epithelial cells. Radiolabeled high-affinity peptides can be used to target the alpha(v)beta(3) integrin and visualize areas of vascular damage. Advances in technology such as the micro-single photon emission computed tomography (microSPECT) have the potential to overcome the drawbacks of older CT and MRI methodologies, such as lack of biologically relevant ligands and compatible blood pool contrast agents for imaging. Despite these advances in imaging technology, the small size of atheromatous lesions makes it difficult to detect using external imaging techniques. Therefore, recently there has been renewed interest in the use of intravascular catheter-based radiation detectors.
Blankenberg
Francis G
FG
Department of Radiology/Division of Pediatric Radiology, Lucile Salter Packard Children's Hospital, Stanford, California, USA. blankenb@stanford.edu
Mari
Carina
C
Strauss
H William
HW
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D001161:Arteriosclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology*; D018932:Chemokine CCL2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D011868:Radioisotopes; D011875:Radionuclide Angiography; D019275:Radiopharmaceuticals / Q000737:chemistry; D013004:Somatostatin / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000379:methods*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D017304:Annexin A5; D018932:Chemokine CCL2; D039302:Integrin alphaVbeta3; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D013004:Somatostatin