by Scott Haller, MS
Medical advancements must bear scrutiny—including the presumed unlimited promise of stem cell-based therapies. Fortunately, that scrutiny is possible through many assays, including non-invasive imaging methods that provide crucial data on biodistribution of these potential new treatments.
Tracking the distribution and fate of implanted or transplanted stem cells is important to understanding where in an organism a cellular-based treatment goes, how long it stays, and how it engages the targeted organ or tissue. Molecular imaging assessments of such therapeutics using PET (positron emission tomography) or SPECT (single-photon emission computerized tomography), which we apply in the Translational Imaging Center, allow us to conduct non-invasive in vivo imaging with repeated measures over several time points using a single animal subject. These are highly effective alternatives to traditional ex vivo biodistribution assessments of such therapeutics which require a greater number of animal subjects assessed over multiple time points. Additional non-invasive imaging assessments include fluorescent imaging probes and /or and magnetic resonance imaging (MRI), which will not be discussed herein.
In the conduct of PET- or SPECT- based studies evaluating a cellular-therapeutic, there are two primary methods of tracking these therapies: direct labeling of a cellular component (internal or integral membrane) or indirect radiotracer directed against a product of the therapeutic activity.
Direct labeling involves placing a marker on the surface or inside the cellular therapeutic prior to exposure to the animal model. Markers, or radioisotopes, are useful for PET and SPECT imaging, and include examples such as Indium-111 oxyquinoline (indium oxine), zirconium-89 or fludeoxyglucose F18. Each of these markers provides differing mechanisms or solutions for labeling the therapeutics and a variety of applications, which are primarily driven by the half-life and available labeling chemistries unique to each.
Indirect labeling, on the other hand, looks at measures of biodistribution that don’t involve attaching a label to the cell itself. This may involve a radiotracer that has binding affinity to the cell’s target receptor, or it may involve identifying certain biomarkers such as specific activity within a pathway when a cell line is activated. Another indirect method is using a reporter gene, which is a gene inserted into a cell’s genetic sequence that makes an easily detected product that can help determine levels of activity. Examples of common reporters used in cell-based therapies include the herpes simplex 1 virus thymidine kinase (HSV-1tk) reporter and the sodium iodine symporter (NIS) reporter.
When the selected reporter gene’s transcription pattern is known and product expressed, the expressed gene product can be labeled with an appropriate radioisotope/radiotracer, must have binding affinity to the gene product, and tracked using PET or SPECT. Thus, a researcher can see how a particular cell line integrates with the targeted tissues.
While not yet widely done, tracking cell-based therapeutics through molecular imaging is rapidly coming into its own. It offers great advantages and insights into stem cell treatments, as well as applications beyond tracking biodistribution, such as determining proof of concept for target engagement efficacy.
With our new Translational Imaging Center, MPI Research and partners stand at the forefront of this evolving discipline in preclinical research, offering Sponsors a valuable edge in quality, speed, and cost. Scott Haller, MS, Director, Imaging and Cellular & Molecular Biology, MPI Research. To learn more about the advantages of the Translational Imaging Center at MPI Research, contact us at firstname.lastname@example.org.