Development of a Lensless Radiomicroscope for Cellular-Resolution Radionuclide Imaging

Abstract

The action of radiopharmaceuticals takes place at the level of cells. However, existing radionuclide assays can only measure uptake in bulk or in small populations of single cells. This potentially hinders the development of effective radiopharmaceuticals for disease detection, staging, and treatment. Methods: We have developed a new imaging modality, the lensless radiomicroscope (LRM), for in vitro, cellular-resolution imaging of β- and α-emitting radionuclides. The palm-sized instrument is constructed from off-the-shelf parts for a total cost of less than $100, about 500 times less than the radioluminescence microscope, its closest equivalent. The instrument images radiopharmaceuticals by direct detection of ionizing charged particles via a consumer-grade complementary metal-oxide semiconductor detector. Results: The LRM can simultaneously image more than 5,000 cells within its 1 cm² field of view, a 100-times increase over state-of-the-art technology. It has spatial resolution of 5 μm for brightfield imaging and 30 μm for ¹⁸F positron imaging. We used the LRM to quantify ¹⁸F-FDG uptake in MDA-MB-231 breast cancer cells 72 h after radiation treatment. Cells receiving 3 Gy were 3 times larger (mean = 3,116 μm²) than their untreated counterparts (mean = 940 μm²) but had 2 times less ¹⁸F-FDG per area (mean = 217 Bq/mm²), a finding in agreement with the clinical use of this tracer to monitor response. Additionally, the LRM was used to dynamically image the uptake of ¹⁸F-FDG by live cancer cells, and thus measure their avidity for glucose. Conclusion: The LRM is a high-resolution, large-field-of-view, and cost-effective approach to image radiotracer uptake with single-cell resolution in vitro.