Development of a lensless radiomicroscope for cellular-resolution radionuclide imaging.

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 beta- and alpha-emitting radionuclides. The palm-sized instrument is constructed from off-the-shelf parts for a total cost of <$100, about 500X less than the radioluminescence microscope, its closest equivalent. The instrument images radiopharmaceuticals by direct detection of ionizing charged particles via a consumer-grade CMOS detector. Results: The LRM can simultaneously image >5k cells within its 1 cm 2 field-of-view, a 100X increase over state-of-the-art technology. It has spatial resolution of 5 µm for brightfield imaging and 30 µm for 18 F positron imaging. We used the LRM to quantify 18 F-fluorodeoxyglucose (FDG) uptake in MDA-MB-231 breast cancer cells 72 hours after radiation treatment. Cells receiving 3 Gy were 3X larger (mean = 3116 µm 2 ) than their untreated counterparts (mean = 940 µm 2 ) but had 2X less 18 F-FDG per area (mean = 217 Bq/mm 2 ), 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 18 F-FDG by live cancer cells, and thus measure their avidity for glucose. Conclusion: The LRM is a high-resolution, large-FOV, and cost-effective approach to image radiotracer uptake with single-cell resolution in vitro.