Abstract
Cell-based therapies, such as adoptive immunotherapy and stem-cell therapy, have received considerable attention as novel therapeutics in oncological research and clinical practice. The development of effective therapeutic strategies using tumor-targeted cells requires the ability to determine in vivo the location, distribution, and long-term viability of the therapeutic cell populations as well as their biological fate with respect to cell activation and differentiation. In conjunction with various noninvasive imaging modalities, cell-labeling methods, such as exogenous labeling or transfection with a reporter gene, allow visualization of labeled cells in vivo in real time, as well as monitoring and quantifying cell accumulation and function. Such cell-tracking methods also have an important role in basic cancer research, where they serve to elucidate novel biological mechanisms. In this Review, we describe the basic principles of cell-tracking methods, explain various approaches to cell tracking, and highlight recent examples for the application of such methods in animals and humans.
Key Points
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Cell tracking has long been performed in the form of nonspecific labeling of white blood cells with either 111In-oxiquinolone or 99mTc-HMPAO, mostly to detect sites of infection
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Novel cell-tracking techniques are based on vastly different principles and employ various detection methods, including MRI, PET, and optical imaging; each is associated with individual advantages and limitations
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Direct labeling of cells only allows short-term tracking, whereas reporter genes (indirect labeling) can be employed for long-term tracking of transfected cells
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Completed and ongoing clinical trials involve, for example, the direct labeling of blood cells with contrast agents or the indirect labeling of T cells with PET reporter genes
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Future clinical applications of cell tracking will likely rely on PET, MRI, or combined MRI–PET to merge the complementary whole-body molecular, functional, and anatomical information provided by these methods
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M. F. Kircher and J. Grimm researched data for the article and provided substantial contributions to the discussion of content. All authors wrote the article, and reviewed and edited the manuscript before submission.
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S. S. Gambhir is stockholder/director of Cellsight, Endra, Enlight, ImaginAB, and Visual Sonics. S. S. Gambhir also received grant/research support from GE Healthcare. M. F. Kircher and J. Grimm declare no competing interests.
Supplementary information
Supplementary Video 1
3D Animation of serial MRI data obtained after adoptive transfer of CLIO-HD-labeled, OT I transgenic CD8+ T cells into a mouse carrying both B16F0 melanomas (in the left side of the body) and B16-OVA melanomas (in the right side of the body). Reproduced with permission from the American Association for Cancer Research © Kircher, M. F. et al. Cancer Res. 63, 6838-6843 (2003). (MOV 2491 kb)
Supplementary Video 2
3D-virtual rendering shows that cytotoxic lymphocytes (CTLs) localize in the lung 2 h after injection. HA-specific CTLs were labeled with 111In-oxine and injected to mice with HA-positive and HA-negative tumor cells. The animation is a representative reconstruction and fusion in OsiriX of the SPECT and CT recordings. Reprinted with permission from the National Academy of Sciences © Pittet, M. J. et al. Proc. Natl Acad. Sci. USA 104, 12457–12461 (2007). (MOV 353 kb)
Supplementary Video 3
3D-virtual rendering shows that a large fraction of administered cytotoxic lymphocytes (CTLs) accumulate in the spleen, liver, and kidney 24 h after injection. HA-specific CTLs were labeled with 111In-oxine and injected to mice with HA-positive and HA-negative tumor cells. The animation is a representative reconstruction in OsiriX of the SPECT and CT recordings. Reprinted with permission from the National Academy of Sciences © Pittet, M. J. et al. Proc. Natl Acad. Sci. USA 104, 12457–12461 (2007). (MOV 324 kb)
Supplementary Video 4
3D-virtual rendering shows that cytotoxic lymphocytes (CTLs) preferentially accumulate in HA-positive tumors 24 h after injection. HA-specific CTLs were labeled with 111In-oxine and injected to mice with HA-positive and HA-negative tumor cells. The animation is a representative reconstruction in OsiriX of the SPECT and CT recordings. Reprinted with permission from the National Academy of Sciences © Pittet, M. J. et al. Proc. Natl Acad. Sci. USA 104, 12457–12461 (2007). (MOV 401 kb)
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Kircher, M., Gambhir, S. & Grimm, J. Noninvasive cell-tracking methods. Nat Rev Clin Oncol 8, 677–688 (2011). https://doi.org/10.1038/nrclinonc.2011.141
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DOI: https://doi.org/10.1038/nrclinonc.2011.141
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