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Cell tracking in vivo with MRI oxide (SPIO) label that is composed of he ethically and politically embat10,000–100,000 iron atoms surrounded tled race to develop cellular theraby covalently bound dextran polysacchapies, with the hope of curing a wide rides. SPIO labels have been approved range of illnesses from cancer to diaby the U.S. Food and Drug Administrabetes, has been hindered further by the tion as an MRI contrast agent in the absence of a high-resolution technology liver but not yet as a cell contrast agent. to track the progress of therapeutic cells underneath a patient’s skin. Now, for the first time in humans, researchers have successfully used MRI to monitor the delivery and migration of therapeutic cells (Nat. Biotech. 2005, 23, 1407– 1413). Jolando de Vries and Carl Figdor of the Nijmegen Center for Molecular Life Sciences (The Netherlands) led the team and After vaccination Before vaccination worked in collaboration with clinical colleagues from the UniversiIn vivo MRI image of a lymph node (circled) before and ty Hospital St. Radboud (The after an injection of SPIO-labeled dendritic cells. Netherlands) and Jeff Bulte at the The cells were allowed to mature and Johns Hopkins University School of were subsequently “pulsed” with melaMedicine. noma peptides, which were designed to In this study, dendritic cells, a type of mimic melanoma tumors. The underlying immune cell, were loaded with tumor logic for a cancer vaccine, according to antigens and magnetic nanoparticles ex Bulte, is that “cancer is essentially the invivo, injected into the lymph nodes of ability of the immune system to completestage III melanoma patients, and tracked ly recognize the cancer as foreign.” The by MRI for up to two months. David hope is that these fortified dendritic cells Bluemke, a professor of radiology at will encounter and activate T cells, thus Johns Hopkins University School of evoking an amplified immune response. Medicine, believes that this approach Currently, cell tracking in vivo is limgives researchers “the ability to monitor and assess the efficacy of these new thera- ited to radioisotope imaging, so the researchers compared their method with pies as well as help us understand what this standard. A batch of dendritic cells cellular therapy is.” loaded with melanoma peptides was laThe researchers extracted peripheral beled with 111In-oxine, and a 1:1 mixblood mononuclear cells, precursors of dendritic cells, from eight patients parture of these and the SPIO-labeled denticipating in a cancer-vaccine clinical dritic cells were injected back into the study. The cells were coaxed into an lymph nodes of the melanoma patients “immature” state, which makes them from which the precursors were origireceptive to the uptake of foreign molenally culled. The progress of the modicules. Then, they were exposed to fied dendritic cells was closely attended ferumoxide, a superparamagnetic iron by both MRI and scintigraphy.
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In the presence of SPIO-labeled cells, the lymph nodes, which usually are bright relative to their surrounding tissues, appeared black. The researchers observed this change first in the lymph nodes where the SPIO-labeled cells were administered and then, as the cells began to migrate, in neighboring lymph nodes. In four of the eight patients, the lymph node failed to dim, and the researchers concluded that the injections had not reached the targets. On the basis of scintigraphy, the injections appeared, falsely, to have been accurately delivered. Furthermore, by using MRI rather than scintigraphy, which could not resolve lymph nodes that were close together, the researchers identified more lymph nodes visited by the therapeutic dendritic cells. Hy Livitsky, professor of oncology at Johns Hopkins University School of Medicine, agrees that MRI cell tracking offers advantages over scintigraphy in terms of resolution. But he adds that the dendritic cells were a special case because they were terminally differentiated— stopped dividing—when the label was injected. Most cell types will continue to divide, and this will dilute the SPIO labels and reduce the visibility of the signal. Then again, “Ultimately, you want the contrast agent to disappear, because we’d like to go back later and use MRI to interrogate the system,” says Joseph Frank, chief of the Laboratory of Diagnostic Radiology Research at the National Institutes of Health. This study, he adds, shows that SPIO labeling is the best available means to answer the dire questions that these burgeoning cellular therapies pose: “When should we give cells, and where do they go?” a —Erika Gebel COURTESY OF JELLE O. BARENTZ
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© 2006 AMERICAN CHEMICAL SOCIETY
