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.

放射性药物的作用发生在细胞水平。然而，现有的放射性核素测定只能测量大量或少量单细胞的吸收。这可能会阻碍用于疾病检测、分期和治疗的有效放射性药物的开发。方法：我们开发了一种新的成像方式，即无透镜放射显微镜 (LRM)，用于对 β 和 α 发射放射性核素进行体外细胞分辨率成像。这种手掌大小的仪器由现成的部件制成，总成本不到 100 美元，比最接近的放射发光显微镜便宜约 500 倍。该仪器通过消费级互补金属氧化物半导体探测器直接检测电离带电粒子来对放射性药物进行成像。结果： LRM 可以在 1 cm ²视野内同时对 5,000 多个细胞进行成像，比最先进的技术提高了 100 倍。明场成像的空间分辨率为 5 μm， ¹⁸ F 正电子成像的空间分辨率为 30 μm。我们使用 LRM 来量化放射治疗后 72 小时 MDA-MB-231 乳腺癌细胞中¹⁸ F-FDG 的摄取。接受 3 Gy 照射的细胞比未处理的细胞（平均值 = 940 μm ² ）大 3 倍（平均值 = 3,116 μm ² ），但每个区域的¹⁸ F-FDG 少 2 倍（平均值 = 217 Bq/mm ² ），这一发现在同意临床使用该示踪剂来监测反应。此外，LRM 用于动态成像活癌细胞对¹⁸ F-FDG 的摄取，从而测量它们对葡萄糖的亲合力。 结论： LRM 是一种高分辨率、大视场且经济高效的体外单细胞分辨率放射性示踪剂摄取成像方法。