Abstract
The radiotracer 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) is commonly used to measure cell proliferation in vivo. As a marker of cell proliferation, 18F-FLT is expected to be differentially taken up by arrested and actively dividing cells, but positron emission tomography (PET) only measures aggregate uptake by tumor cells and therefore the single-cell distribution of 18F-FLT is unknown. We use a novel in vitro radioluminescence microscopy technique to measure the differential distribution of 18F-FLT radiotracer with single-cell precision. Methods: Using radioluminescence microscopy, we image the absolute uptake of 18F-FLT in live MDA-MB-231 cells grown under different serum conditions. We then compare 18F-FLT uptake to a standard measure of cell proliferation, using fluorescence microscopy of EdU incorporation in fixed cells. Results: According to EdU staining, few cells (1%) actively cycle under serum deprivation while a majority of them (71%) do under 20% serum. The distribution of 18F-FLT reflects this dynamic. At 0% serum, uptake of 18F-FLT is heterogeneous but relatively low. At 20% serum, a subpopulation of 18F-FLT-avid cells, representing 61% of the total population, emerges. Uptake of 18F-FLT in this population is fivefold higher than in the remainder of the cells. Such a dichotomous distribution is not typically observed with other radiotracers such as 18F-FDG. Conclusion: These results suggest that increased 18F-FLT uptake by proliferating cells is due to a greater fraction of 18F-FLT-avid cells rather than a change in 18F-FLT uptake by individual cells. This finding is consistent with the fact that 18F-FLT uptake is mediated by expression of thymidine kinase 1 (TK1), which is expressed more highly in actively dividing cells. Overall, these findings suggest that, within the same patient, changes in 18F-FLT uptake reflect changes in the number of actively dividing cells, provided other parameters remain the same.
- Image Processing
- Molecular Imaging
- Oncology: Breast
- FLT
- cancer proliferation
- microscopy
- nucleoside analogues
- radionuclide imaging
- Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.