High-Resolution Radioluminescence Microscopy of 18F-FDG Uptake by Reconstructing the β-Ionization Track

Radioluminescence microscopy is a new method for imaging radionuclide uptake by single live cells with a fluorescence microscope. Here, we report a particle-counting scheme that improves spatial resolution by overcoming the beta-range limit. Methods: Short frames (10 mu s(-1) s) were acquired using a high-gain camera coupled to a microscope to capture individual ionization tracks. Optical reconstruction of the beta-ionization track (ORBIT) was performed to localize individual beta decays, which were aggregated into a composite image. The new approach was evaluated by imaging the uptake of F-18-FDG in nonconfluent breast cancer cells. Results: After image reconstruction, ORBIT resulted in better definition of individual cells. This effect was particularly noticeable in small clusters (2-4 cells), which occur naturally even for nonconfluent cell cultures. The annihilation and Bremsstrahlung photon background signal was markedly lower. Single-cell measurements of F-18-FDG uptake that were computed from ORBIT images more closely matched the uptake of the fluorescent glucose analog (Pearson correlation coefficient, 0.54 vs. 0.44, respectively). Conclusion: ORBIT can image the uptake of a radiotracer in living cells with spatial resolution better than the beta range. In principle, ORBIT may also allow for greater quantitative accuracy because the decay rate is measured more directly, with no dependency on the beta-particle energy.