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Science to Practice |
Department of Radiology, Hôpital Européen Georges Pompidou and Inserm U 494, School of Medicine Paris 5, Paris 75908, France
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In vivo visualization of transplanted cells (cellular imaging) with noninvasive techniques such as magnetic resonance (MR) imaging is of growing interest to radiologists. The aim is to monitor the effectiveness of new cellular therapies and to see how transplanted cells migrate through the body.
Target cells are labeled with superparamagnetic particles that have high T2* properties (1). High-field-strength imaging is usually required to increase contrast and spatial resolution (2). After local injection in the myocardium, for example, labeled cells are easy to visualize because of their high local density (3). However, detection of transplanted cells in a specific organ after systemic injection is more challenging (4). In this issue of Radiology, Daldrup-Link et al (5) describe an elegant way of depicting hematopoietic cells after systemic injection by using a clinical MR imaging system operating at 1.5 T.
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Superparamagnetic nanoparticles are currently used for liver imaging and will soon be available for other macrophage-based applications such as imaging lymph nodes or plaque. When used to label cells in vitro, the efficiency depends on the cell type and is generally poor with nonmacrophagic cells. Optimized protocols that use various "transfecting" agents have been developed, notably to label neural and mesenchymal cells (6,7).
Daldrup-Link et al (5) labeled human hematopoietic progenitor cells by means of simple incubation with ferumoxides and by using a new anionic particle and a liposomal transfecting agent. After intravenous injection of (1.0–3.0) x 107 labeled cells into mice, the authors found that the cells migrated to the liver and spleen and gradually homed to bone marrow, as indicated by a marked decline in the femoral signal intensity at 24 and 48 hours. In contrast, simple injection of only contrast agent resulted in a decline of the liver and spleen signal intensity. Similar results were obtained with two contrast agents, and results of precise histologic correlation studies confirmed that the loss of signal intensity in bone marrow was due to homing of labeled cells and not to the release of free particles.
The Practice
Clinical use.—Cellular therapies can be used to replace dead tissue (bone marrow transplantation, mesenchymal cell injection after myocardial infarction, use of neuronal cells in neurodegenerative diseases), to kill cancer cells, or to replace a deficient gene, and also as a diagnostic tool (detection of deep abscesses with labeled leukocytes).
The development of an appropriate imaging technique, with optimized cell labeling and MR imaging conditions, will be useful in all these settings in that it will enable monitoring of the effectiveness of cell transplantation, homing, and differentiation.
Future opportunities and challenges.—The labeling procedure must be nontoxic; that is, it must not affect differentiation or functionality. The use of an existing, well-characterized labeling agent has obvious advantages in this respect. Sensitivity is a major challenge, especially in settings where few therapeutic cells are injected. It will probably be impossible to track single cells, but homing to specific anatomic sites should be detectable with optimized imaging and labeling techniques. The duration of detectability must also be taken into account and will depend on the rate of cell division—from a few weeks for neural cells or hepatocytes to days for rapidly dividing cells.
Summary
Daldrup-Link et al (5), after labeling hematopoietic cells with superparamagnetic particles in vitro and injecting them intravenously into mice, found that specific homing to bone marrow could be observed after 24 and 48 hours by using a clinical magnet and optimized T2*-weighted MR imaging sequences. Further optimization of this technique will allow us to monitor labeled cells injected intravenously for diagnostic or therapeutic purposes.
REFERENCES
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