Bright Lu₂O₃:Eu Thin‐Film Scintillators for High‐Resolution Radioluminescence Microscopy

Abstract

We investigate the performance of a new thin-film Lu2O3:Eu scintillator for single-cell radionuclide imaging. Imaging the metabolic properties of heterogeneous cell populations in real time is an important challenge with clinical implications. We have developed an innovative technique called radioluminescence microscopy, to quantitatively and sensitively measure radionuclide uptake in single cells. The most important component of this technique is the scintillator, which converts the energy released during radioactive decay into luminescent signals. The sensitivity and spatial resolution of the imaging system depend critically on the characteristics of the scintillator, i.e. the material used and its geometrical configuration. Scintillators fabricated using conventional methods are relatively thick, and therefore do not provide optimal spatial resolution. We compare a thin-film Lu2O3:Eu scintillator to a conventional 500 μm thick CdWO4 scintillator for radioluminescence imaging. Despite its thinness, the unique scintillation properties of the Lu2O3:Eu scintillator allow us to capture single positron decays with over fourfold higher sensitivity, a significant achievement. The thin-film Lu2O3:Eu scintillators also yield radioluminescence images where individual cells appear smaller and better resolved on average than with the CdWO4 scintillators. Coupled with the thin-film scintillator technology, radioluminescence microscopy can yield valuable and clinically relevant data on the metabolism of single cells.

Single-Cell Characterization of 18F-FLT Uptake with Radioluminescence Microscopy

“…Radioluminescence microscopy can visualize the uptake of PET tracers in vitro , with single-cell resolution, in a multi-modal microscopy environment that also includes fluorescence and brightfield imaging capabilities (14, 15). While the method has been applied to various radiotracers such as FHBG (15), FDG (14), and radiolabeled antibodies, the uptake of FLT has previously not been measured in single cells. With this study, we aim to demonstrate that FLT uptake is a specific marker of proliferation at the single-cell level.…”

Optical Imaging of Ionizing Radiation from Clinical Sources

“…4A and 4B). The thinner Lu 2 O 3 :Eu plate has a higher photon yield and emissions in the green-red region of the visible spectrum, where typical charge-coupled devices have greater quantum efficiency compared to blue emissions by CdWO 4 (36). In a practical demonstration of RLM, 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT) uptake was imaged in MDA-MB-231 cells grown under different serum conditions and compared to fluorescence microscopy of 5-ethynyl-2'-deoxyuridine (EdU) incorporation in fixed cells, a standard measure of cell proliferation (Fig.…”

“…Red and green arrows indicate cells with negative and positive signals, respectively. (A–B) and (C) adapted with permission of (36) and (37), respectively.…”

In silico optimization of radioluminescence microscopy

“…Radioluminescence microscopy (RLM), an emerging technique for high‐resolution radionuclide imaging, has the capability to visualize positron emission tomography (PET) radiotracers at the single cell level . Unlike other optical imaging modalities (eg, bioluminescence and fluorescence imaging), radioluminescence imaging detects the dim light resulting from the interaction of ionizing particles with a scintillator substrate.…”

“…Given the challenging nature of imaging radionuclides at the single‐cell level with high sensitivity, the performance of RLM in terms of spatial resolution and sensitivity must be as high as possible. Currently, the design of the microscope (eg, the parameters of the microscopy objective, scintillator and camera) has been optimized empirically, through trial and error . For instance, a 10‐μm thin Lu 2 O 3 scintillator has been used in some experiments to enhance spatial resolution and sensitivity.…”