Ralph Weissleder, M.D., Ph.D., professor, department of radiology at Harvard Medical School and director, Center for Molecular Imaging Research at Massachusetts General Hospital, described his research on in vivo imaging of drug effects and the results of experiments designed to understand the biological basis of tumor cell interaction with host cells.
A primary goal of this work is to translate the use of intravital microscopy and injectable fluorescent probes from the research laboratory to the clinic for the purpose of assessing the effects of chemotherapeutic agents on tumor and normal cells and identifying more targeted cancer therapies.
Advances in the adaptation of cell-based assays to intravital imaging in the mouse have demonstrated fundamental differences between what is seen in vitro versus in vivo. Dr. Weissleder emphasized three specific benefits that intravital microscopy offers cancer researchers: the potential to observe physiological responses, to study heterogeneity within populations of cancer cells or between cellular processes, and to image drug responses. How best to achieve these benefits—what cell and tumor types to study, how long to image and follow cell populations, and what imaging parameters are optimal, for example—are all questions that require further study.
Tumors can be imaged in situ by applying various techniques including the use of “stick” lenses, or microscope objectives that enable “keyhole” imaging, as well as imaging modalities such as laser-scanning confocal or multiphoton microscopy. Studying drug responses in tumors requires high spatial resolution to observe nuclear phenotypes and detect nuclear division, explained Dr. Weissleder.
Whole tumor imaging can be achieved at high resolution by imaging tumor slices and then combining the individual images—a process called “image stitching.”
As drug responses evolve over time and may be heterogeneous across tumor cell populations, the ability to do time-lapse imaging and sequential studies in the same animal over multiple time points is important. This presents a particular challenge as tumors are dynamic structures; it requires the development of methods and technologies that will allow researchers to image the same group of cells in vivo over a period of hours to days.
Cost can be a significant barrier to entry into the emerging field of intravital imaging. While microscopy systems are available in a range of complexity, capabilities, and costs, with personal confocal microscopes available for as low as $100,000, and multiphoton imaging systems for $200,000, instrument costs are only one component of the overall expense. Additional infrastructure needs to build and maintain small animal and surgical facilities must also be considered.