Radioluminescence microscopy is a newly developed method for imaging radionuclide uptake in live single cells. Current methods of radiotracer imaging are limited to measuring the average radiotracer uptake in large cell populations and, as a result, lack the ability to quantify cell-to-cell variations. With the new radio- luminescence microscopy technique, however, it is possible to visualize radiotracer uptake within individual cells in a fluorescence microscope environment. The goal of this project is to develop a revolutionary innovation in a key component used in this technique. This key part in the radioluminescence microscopy imaging system is the scintillator that converts ionizing beta radiation into optical photons that are imaged with a CCD camera. In this work, an improved scintillator will be developed, specifically for use in a radioluminescence microscopy system that will offer unprecedented sensitivity and spatial resolution. Such a technological advance has the potential for widespread use in research and in hospitals, providing a means to characterize how properties specific to individual cells (e.g. gene expression, cell cycle, cell damage, and cel morphology) affect the uptake and retention of radiotracers. Higher spatial resolution will allow single cells to be probed in situ, in dense tissue sections, and will dramatically improve the throughput of the instruments, allowing thousands of cells to be imaged at once. These new capabilities will be critical to help researchers better understand the behavior of rare single cels such as stem cells or drug-resistant cells. The objectives of this Phase I project is the demonstrate the feasibility of successfully depositing of thin (micron-scale) films of a highly dense transparent scintillator, europium-activated lutetium oxide (Lu2O3:Eu). This material has the highest density (9.5 g/cm3) of any known scintillator, high effective atomic number (67.3), excellent light output, and an emission wavelength (610 nm) for which Si sensors have a very high quantum efficiency. Select scintillator specimens will be integrated into a radioluminescence microscope demonstrating improved performance in this exciting new imaging system. Ultimately, the goal is to commercialize this technology as a radioluminescence-enabled imaging dish, which will have a standard form factor but will include a thin coating of the Lu2O3:Eu scintillator at the bottom. As such, the technological innovation will provide a valuable new tool to researchers allowing unprecedented localization of radiotracer uptake down to single living cells. This new innovative technology will have widespread use as an addition to current fluorescence microscope instruments in use today and thus will have great commercial potential.
The goal of the proposed research is to develop a very high performance radioluminescence microscope for imaging radionuclide uptake in live single cells. Among other benefits, this technological advance has the potential for widespread use in research and in hospitals, providing a means to characterize how properties specific to individual cells (e.g. gene expression, cell cycle, cell damage, and cell morphology) affect the uptake and retention of radiotracers. Because of the prominent role played by PET in oncology, radioluminescence microscopy may also become a routine technique in cancer biology, for instance, to study the behavior of distinct cell subpopulations within a tumor, such as the cancer stem cells or drug- resistant cells. In hematology, the microscope could be used to characterize the properties of single immune cells. Last, this new technique will benefit the development of new imaging and therapeutic radiopharmaceuticals since it will allow researchers to more precisely measure the uptake of a radiopharmaceutical in single cells.