Single-Cell Imaging Using Radioluminescence Microscopy Reveals Unexpected Binding Target for [18F]HFB

Kiru, Louise; Kim, Tae Jin; Shen, Bin; Chin, Frederick T.; Pratx, Guillem

doi:10.1007/s11307-017-1144-0

Cited by 10 publications

(7 citation statements)

References 43 publications

(53 reference statements)

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“…The mechanisms behind the difference in retention between the cell surface labeling agents [ 18 F]HFB/[ 124 I]HIB and [ 18 F]SFB were not explored, but it is possible than protein-rich areas of the membrane (to which [ 18 F]SFB is more likely to bind) are more frequently recycled or that surface protein-bound radiolabels are cleaved by extracellular proteases. [ 18 F]HFB was found to preferentially bind to disrupted membrane fragments on dead cells over live intact cells . This could be a potential drawback for in vivo cell tracking with this agent, as dead cells can have different biodistribution profiles compared to live cells, leading to misinterpretation of the images .…”

Section: Chemical Probes For Ex Vivo Direct Cell Radiolabelingmentioning

confidence: 99%

Direct Cell Radiolabeling for in Vivo Cell Tracking with PET and SPECT Imaging

et al. 2022

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The arrival of cell-based therapies is a revolution in medicine. However, its safe clinical application in a rational manner depends on reliable, clinically applicable methods for determining the fate and trafficking of therapeutic cells in vivo using medical imaging techniquesknown as in vivo cell tracking. Radionuclide imaging using single photon emission computed tomography (SPECT) or positron emission tomography (PET) has several advantages over other imaging modalities for cell tracking because of its high sensitivity (requiring low amounts of probe per cell for imaging) and whole-body quantitative imaging capability using clinically available scanners. For cell tracking with radionuclides, ex vivo direct cell radiolabeling, that is, radiolabeling cells before their administration, is the simplest and most robust method, allowing labeling of any cell type without the need for genetic modification. This Review covers the development and application of direct cell radiolabeling probes utilizing a variety of chemical approaches: organic and inorganic/coordination (radio)chemistry, nanomaterials, and biochemistry. We describe the key early developments and the most recent advances in the field, identifying advantages and disadvantages of the different approaches and informing future development and choice of methods for clinical and preclinical application.

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Section: Chemical Probes For Ex Vivo Direct Cell Radiolabelingmentioning

confidence: 99%

Direct Cell Radiolabeling for in Vivo Cell Tracking with PET and SPECT Imaging

et al. 2022

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“…In conclusion, we have developed a method to fabricate and characterize thin-film scintillator dishes for radioluminescence microscopy. Radioluminescence microscopy is an important technique that has already been used for microscopy applications beyond FDG imaging; radioluminescence has shed light on the localization characteristics of hexadecyl-4-[ 18 F]fluorobenzoate ([ 18 F]HFB) 19 as well as the distribution pattern of 3'-deoxy-3'-[ 18 F]fluorothymidine ( 18 F-FLT) in proliferative vs. non-proliferative cells 3 .…”

Section: Discussionmentioning

confidence: 99%

Development and characterization of a scintillating cell imaging dish for radioluminescence microscopy

Sengupta

Kim

Almasi

et al. 2018

Analyst

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Radioluminescence microscopy is an emerging modality that can be used to image radionuclide probes with micron-scale resolution. This technique is particularly useful as a way to probe the metabolic behavior of single cells and to screen and characterize radiopharmaceuticals, but the quality of the images is critically dependent on the scintillator material used to image the cells. In this paper, we detail the development of a microscopy dish made of a thin-film scintillating material, Lu2O3:Eu, that could be used as the blueprint for a future consumable product. After developing a simple quality control method based on long-lived alpha and beta sources, we characterize the radioluminescence properties of various thin-film scintillator samples. We find consistent performance for most samples, but also identify a few samples that do not meet the specifications, thus stressing the need for routine quality control prior to biological experiments. In addition, we test and quantify the transparency of the material, and demonstrate that transparency correlates with thickness. Finally, we evaluate the biocompatibility of the material and show that the microscopy dish can produce radioluminescent images of live single cells.

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“…Previously, we developed radioluminescence microscopy (RLM) as a new method to image radiotracer uptake in a microscopic environment. RLM allows researchers to quantitatively image the transport kinetics of radioactive molecules with single-cell resolution and also perform fluorescence microscopy using the same platform. , The modality has been used to evaluate novel molecular imaging probes , and investigate the biological response of clinical PET tracers. , A comprehensive literature review by Liu and Lan summarizes the specific advantages of RLM and other radionuclide bioassays …”

Section: Introductionmentioning

confidence: 99%

Microfluidics-Coupled Radioluminescence Microscopy for In Vitro Radiotracer Kinetic Studies

Kim

Bick

et al. 2021

Anal. Chem.

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Integrated bioassay systems that combine microfluidics and radiation detectors can deliver medical radiopharmaceuticals to live cells with precise timing, while minimizing radiation dose and sample volume. However, the spatial resolution of many radiation imaging systems is limited to bulk cell populations. Here, we demonstrate microfluidics-coupled radioluminescence microscopy (μF-RLM), a new integrated system that can image radiotracer uptake in live adherent cells growing inside microincubators with spatial resolution better than 30 μm. Our method enables on-chip radionuclide imaging by incorporating an inorganic scintillator plate (CdWO 4 ) into a microfluidic chip. We apply this approach to investigate the factors that influence the dynamic uptake of [ 18 F]fluorodeoxyglucose (FDG) by cancer cells. In the first experiment, we measured the effect of flow on FDG uptake of cells and found that a continuous flow of the radiotracer led to fourfold higher uptake than static incubation, suggesting that convective replenishment enhances molecular radiotracer transport into cells. In the second set of experiments, we applied pharmacokinetic modeling to show that lactic acidosis inhibits FDG uptake by cancer cells in vitro and that this decrease is primarily due to downregulation of FDG transport into the cells. The other two rate constants, which represent FDG export and FDG metabolism, were relatively unaffected by lactic acidosis. Lactic acidosis is common in solid tumors because of the dysregulated metabolism and inefficient vasculature. In conclusion, μF-RLM is a simple and practical approach for integrating high-resolution radionuclide imaging within standard microfluidics devices, thus potentially opening venues for investigating the efficacy of radiopharmaceuticals in in vitro cancer models.

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Single-Cell Imaging Using Radioluminescence Microscopy Reveals Unexpected Binding Target for [18F]HFB

Cited by 10 publications

References 43 publications

Direct Cell Radiolabeling for in Vivo Cell Tracking with PET and SPECT Imaging

Direct Cell Radiolabeling for in Vivo Cell Tracking with PET and SPECT Imaging

Development and characterization of a scintillating cell imaging dish for radioluminescence microscopy

Microfluidics-Coupled Radioluminescence Microscopy for In Vitro Radiotracer Kinetic Studies

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