Cousins at work: How combining medical with optical imaging enhances in vivo cell tracking

Abstract

Microscopy and medical imaging are related in their exploitation of electromagnetic waves, but were developed to satisfy differing needs, namely to observe small objects or to look inside subjects/objects, respectively. Together, these techniques can help elucidate complex biological processes and better understand health and disease. A current major challenge is to delineate mechanisms governing cell migration and tissue invasion in organismal development, the immune system and in human diseases such as cancer where the spatiotemporal tracking of small cell numbers in live animal models is extremely challenging. Multi-modal multi-scale in vivo cell tracking integrates medical and optical imaging. Fuelled by basic research in cancer biology and cell-based therapeutics, it has been enabled by technological advances providing enhanced resolution, sensitivity and multiplexing capabilities. Here, we review which imaging modalities have been successfully used for in vivo cell tracking and how this challenging task has benefitted from combining macroscopic with microscopic techniques.

In Vivo PET Tracking of 89Zr-Labeled Vγ9Vδ2 T Cells to Mouse Xenograft Breast Tumors Activated with Liposomal Alendronate

“…Whole-body imaging is highly useful in this context by enabling in vivo tracking of administered cells. Many techniques exist for non-invasive cell tracking;16, 17, 18 however, only nuclear imaging, and particularly positron emission tomography (PET), provides sensitive and quantitative, whole-body information with adequate spatiotemporal resolution. Hence, methods to radiolabel and track therapeutic cells using positron-emitting radionuclides are likely to become important tools for cell immunotherapy 19 …”

Intravital Imaging of Adoptive T-Cell Morphology, Mobility and Trafficking Following Immune Checkpoint Inhibition in a Mouse Melanoma Model

“…Intravital imaging using multiphoton microscopy is an example of an imaging tool that can be used for the direct visualization and characterization of cell behavior and spatiotemporal dynamics of physiological processes within living organisms. The technique has been used for studying various aspects of innate and adaptive immune responses to cancer, infection and inflammatory disorders at single-cell resolution ( 24 , 25 ), and is complementary to macroscopic imaging techniques for in vivo cell tracking, such as positron emission tomography (PET), single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) ( 26 – 28 ).…”

The Future of Regulatory T Cell Therapy: Promises and Challenges of Implementing CAR Technology

“…The alternative is "indirect cell labeling, " whereby a genetically encoded reporter is ectopically introduced into the cells mostly by viral transduction to ensure genomic integration and thus stable long-term expression; transposon and gene editing represent alternative methodologies (106,107). Reporter genes have critical advantages over direct labeling for cell tracking (99,108). First, the observation period is independent of the contrast agent, for example, not affected by the half-life of a radioisotope.…”