MR Contrast Agents: Past, Recent Trends, and Prospects Department of Diagnostic Radiology, Keio University School of Medicine NICHIDOKU-IHO Vol. 50 No. 1 114 132 (2005) Akihiro Tanimoto, M.D. and Sachio Kuribayashi, M.D. Summary Non-specific extracellular gadolinium chelates have been widely used in contrastenhanced MR imaging. These agents distribute into the intravascular and interstitial spaces and differentially alter tissue contrast through relatively selective enhancement of proton relaxation based on differences in compartmentation, distribution, and residence times of the pharmaceutical. They also allow the evaluation of physiological parameters, such as the status or presence of the blood-brain-barrier or renal function. Meanwhile, liver-specific MR contrast agents have been developed as the first tissue-specific pharmaceuticals to include superparamagnetic iron oxide (SPIO) particles and hepatobiliary paramagnetic agents. SPIO particles are phagocytosed by reticuloendothelial cells in the liver, resulting in negative enhancement of the liver parenchyma on T2- or T2*-weighted imaging. Hepatobiliary paramagnetic agents are partially taken up by hepatocytes, yielding positive sustained enhancement of the liver parenchyma on T1-weighted imaging. These agents have been demonstrated to improve the detection and characterization of hepatic neoplasms, and are expected to simplify the existing multi-step diagnosis in liver imaging. Numerous magneto-pharmaceuticals have been studied as potential tissue-specific MR contrast agents. A wide variety of vector and carrier molecules, including antibodies, peptides, proteins, polysaccharides, liposomes, and cells, have been developed to deliver magnetic labels to specific sites. Macromolecular MR contrast agents (blood pool agents) will be beneficial for improving the quality of MR angiography, for quantitating capillary permeability, and for myocardial perfusion imaging. The permeability of macromolecular tracers may also provide tissue uptake information for both contrast and chemotherapeutic drugs. Dedicated blood pool agents will be available within the next few years. Contrast-enhanced lymphography after interstitial or intravenous injection will be another major step forward in diagnostic imaging. Ultra small SPIO (USPIO) particles have been evaluated in multicenter clinical trials for lymph node MR imaging, and the clinical impact is taken up for discussion. It is likely that USPIO and gadolinium chelates will augment the MRI of atherosclerotic plaques, a systemic inflammatory disease of the arterial wall. Thrombus-specific agents based on gadolinium-labeled peptides are on the doorstep. Gd-porphyrins also can be used as a dual probe for MRI contrast agents and as a radiation sensitizer for neutron capture therapy. This may facilitate tumor detection and treatment planning and potentially improve the safety and efficacy of radiation therapy. Expectations for these new tumor-, pathology-, and receptor-specific agents are high. A series of recent studies indicate that MRI cell tracking has great potential for the evaluation and optimization of stem and progenitor cell therapy. MR tracking of magnetically labeled cells following transplantation or transfusion could determine the distribution of these cells and monitor therapeutic effect. Up to now, SPIO particles appear to be the contrast agent of choice to label stem cells, owing to their biocompatibility and strong effects on proton T2* relaxation. Cell-tracking research has been performed in disease models of the central nervous system and the infarcted myocardium. With its excellent spatial resolution and the ability to track labeled cells over prolonged periods of time, MRI cell tracking is likely to become an important technique. Technical advances in MR imaging will further facilitate the exploitation of tissue-specific MR contrast agents. The past history, recent trends, and prospects of MR contrast agent development are outlined in this review.
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