Development of new thin-film scintillators for high-resolution radioluminescence microscopy

Objectives Radioluminescence microscopy (RLM), a recently introduced method for imaging radiotracers with single-cell resolution, has been demonstrated to work well in cultures with sparse cell distributions. A key limitation to performance is the scintillator that converts the beta particles to optical light photons. The objective of this work is to develop an improved imaging system that utilizes a new thin-film Lu₂O₃:Eu scintillator that provides significantly improved spatial resolution, making it possible to localize radionuclide molecules within single cells even when cells are part of more confluent cell cultures and tissue sections.

Methods The RLM instrument measures the radiotracer uptake in live cells by placing a thin scintillator near the sample. Here we are exploring a new scintillator, Lu₂O₃:Eu, which has improved material properties that translate to significantly improved performance. We fabricated transparent Lu₂O₃:Eu scintillator screens by means of electron beam physical vapor deposition technique (EBPVD). The Lu₂O₃:Eu scintillator films measured about 10 µm in thickness, which dramatically improves spatial resolution since only the beginning of the positron track is captured.

Results To evaluate this new technology, murine breast cancer cells (4T1) were grown on a thin-film scintillator coated with fibronectin. The cells were incubated with FDG (250 Ci/mL, 30 min) and then imaged using RLM. The light output of Lu₂O₃:Eu is high enough for single positron decays to be detected and localized using a sensitive microscope. The resulting reconstructed images demonstrated significantly improved spatial resolution compared to images acquired using a 500 µm thick CdWO₄ scintillator.

Conclusions These results clearly indicate that RLM is a powerful method that can be used for a variety of multi-modal imaging applications. Using thin-film scintillators can significantly improve spatial resolution and lower background in RLM, making single-cell analyses more robust.

Research Support NIH 1R01CA186275-01, and NIH 1R43GM110888-01