Cell tracking provides insights into how cells interact

In nuclear medicine, the non-invasive molecular imaging modalities position emission tomography (PET) and single-photon emission computed tomography (SPECT) are powerful technologies that can be used to track the distribution and fate of cells, to understand where a cellular-based treatment goes, the length of time it remains there and how it interacts with a specific organ or tissue.

To establish the efficacy of a cellular therapy, researchers need to understand the interplay between various factors including cell type, cause of disease, delivery route, cell retention and activation of resident cells. Integrating PET and SPECT into preclinical and clinical trials of cellular therapies has helped to optimize those therapies by enriching scientists’ understanding of how these factors interact.

To perform cellular tracking via PET or SPECT, two main methods are employed: direct labelling and indirect labelling.

In direct labelling, a marker or radioisotope such as indium-111 oxyquinoline or fludeoxyglucose F18 is placed inside or on the surface of the cellular therapeutic ex vivo. The radioisotope enters a cell by active/passive transport and as it decays, it collides with neighboring electrons, resulting in the emission of gamma rays.

Indirect labelling assesses biodistribution without a label being attached to the cell itself. For example, a radiotracer that binds to a target receptor on the cell may be used or when a cell line is activated, the activity within a cellular pathway may be identified. Another indirect method involves labelling cells using specific reporter genes that are inserted into the cell’s genome using a vector. Once integrated within the genome, the reporter genes are transcribed into mRNA and translated and expressed as proteins that can be bound by a radioisotope for signal generation.

The signal generated by either the direct or indirect labeling technique can then be detected and visualized using PET or SPECT.