This project will develop a new pipeline for tracking the migration of single cells in vivo at the whole-body level.
Cell migration is a crucial biological process involved in the pathology and treatment of some of the world’s
most intractable diseases. Stem cell therapy and immunotherapy, for instance, are emerging as viable
treatments for conditions previously thought incurable, such as heart failure and diabetes. Unfortunately, cell
tracking methods remain inadequate to fully capitalize on these recent advances. Currently, cell tracking relies
on imaging the distribution of a specific population of cell through a contrast agent, which is either directly
affixed to the cells or targeted towards an engineered reporter protein. This approach precludes precise
measurement of cell circulation kinetics or migration routes. Furthermore, due to efflux and non-specific
retention, the distribution of the contrast agent does not necessarily match the underlying distribution of cells.
In view of these challenges, we consider a novel approach that has the potential to revolutionize cell tracking.
While current methods aim to track bulk populations of cells, we hypothesize that novel biological insight may
be gained by tracking cells individually, in small numbers, with unprecedented temporal and spatial accuracy.
We will pursue the development of CellGPS, a method capable of tracking the 3D position of individual cells
continuously as these cells migrate through the body of a living subject. To accomplish this goal, we rely on a
previously developed algorithm that can extract the position of a moving cell directly from the raw list-mode
output of a positron emission tomography (PET) scanner. PET is the most sensitive imaging modality available
for whole-body human imaging and, therefore, the ideal imaging modality for this project. Building on extensive
preliminary studies, we plan to pursue the following four specific aims: (1) develop a rapid, safe and robust
strategy for radiolabeling cells; (2) design and build a novel microfluidics pipeline to molecularly profile and
isolate single cells for in vivo tracking; (3) evaluate single-cell tracking as a readout of cell dissemination in an
experimental model of metastatic melanoma; and (4) explore translation of this technology to human imaging
scanners. This project is expected to generate a positive impact for biomedical research both in the pre-clinical
and clinical setting. For instance, single-cell tracking could be used to determine the spatiotemporal kinetics of
cell migration during the earliest phase of the metastatic cascade. The method could also help determine the
dynamic distribution of cells after transplantation for cell-based therapy, which could help predict response and
optimize treatment regimen. This project will achieve critical milestones towards routine and reproducible
tracking of single cells in vivo using PET.