Technical Note: Scintillation well counters and particle counting digital autoradiography devices can be used to detect activities associated with genomic profiling adequacy of biopsy specimens obtained after a low activity <sup>18</sup>F‐<scp>FDG</scp> injection

Kirov, A; Fanchon, Louise M.; Seiter, Daniel; Czmielewski, Christian; Russell, James; Doğan, Snjezana; Carlin, Sean; Pinker-Domenig, Katja; Yorke, Ellen; Schmidtlein, C. Ross; Boyko, Vitaly; Fujisawa, Sho; Manova‐Todorova, Katia; Zanzonico, Pat; Dauer, Lawrence T.; Deasy, Joseph O.; Humm, John L.; Solomon, Stephen B.

doi:10.1002/mp.12836

Cited by 9 publications

(7 citation statements)

References 31 publications

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“…For maximal sensitivity, RLM does not collimate the incoming positrons, thus spatial information is derived from the proximity of the source to the scintillator. A similar problem arises during autoradiography of biopsy samples, where the resolution of the image is also limited by positron range and sample thickness [17,18]. However, the advantage of RLM over autoradiography methods is that RLM can offer multimodal optical microscopy and higherresolution digital radionuclide imaging in a single instrument [12].…”

Section: Discussionmentioning

confidence: 99%

“…In this respect, engineered tumor microenvironments that contain stromal and/or immune cells provide an attractive platform to develop and investigate PET tracers. RLM can image commonly used PET radioisotopes, including 18 F, 68 Ga, 64 Cu, 124 I, and 11 C. As only a small section of the scintillator is in focus during imaging, the larger positron range of some of the above isotopes does not degrade the spatial resolution in RLM. Moreover, therapeutic alpha and beta radiation could be imaged for microdosimetry evaluation of radiopharmaceutical therapy.…”

Section: Discussionmentioning

confidence: 99%

“…To estimate the relative FDG concentration within A549 spheroids (tumor) and the HUVEC microvascular network (stroma), the EMCCD radioluminescence signal was calibrated by imaging a drop of FDG containing a known amount of FDG. Timelapse RLM imaging was performed to record decreasing EMCCD counts, while the radioactivity corresponding to those time points was calculated using the standard 18 F decay curve. The recorded EMCCD signal was found to be linearly correlated to the computed amount of FDG.…”

Section: Quanti Cation Of Fdg Concentrationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High-resolution radioluminescence microscopy of FDG uptake in an engineered 3D tumor-stoma model

Khan

Kim

Yang

et al. 2021

Eur J Nucl Med Mol Imaging

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The increased glucose metabolism of cancer cells is the basis for 18 F-uorodeoxyglucose positron emission tomography (FDG-PET). However, due to its coarse image resolution, PET is unable to resolve the metabolic role of cancer-associated stroma, which often in uences the metabolic reprogramming of a tumor. This study investigates the use of radioluminescence microscopy for imaging FDG uptake in engineered 3D tumor models with high resolution. METHODMulticellular tumor spheroids (A549 lung adenocarcinoma) were co-cultured with GFP-expressing human umbilical vein endothelial cells (HUVECs) within an arti cial extracellular matrix to mimic a tumor and its surrounding stroma. The tumor model was constructed as a 200 µm-thin 3D layer over a transparent CdWO 4 scintillator plate to allow high-resolution imaging of the cultured cells. After incubation with FDG, the radioluminescence signal was collected by a highly sensitive wide eld microscope. Fluorescence microscopy was performed using the same instrument to localize endothelial and tumor cells. RESULTSSimultaneous and co-localized bright eld, uorescence and radioluminescence imaging provided highresolution information on the distribution of FDG in the engineered tissue. The microvascular stromal compartment as a whole took up a large fraction of the FDG, comparable to the uptake of the tumor spheroids. In vitro gamma counting con rmed that A549 and HUVEC cells were both highly glycolytic with rapid FDG-uptake kinetics. Despite the relative thickness of the tissue constructs, an average spatial resolution of 64 ± 4 µm was achieved for imaging FDG. CONCLUSIONOur study demonstrates the feasibility of imaging the distribution of FDG uptake in engineered in vitro tumor models. With its high spatial resolution, the method can separately resolve tumor and stromal components. The approach could be extended to more advanced engineered cancer models but also to surgical tissue slices and tumor biopsies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Quanti Cation Of Fdg Concentrationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

High-resolution radioluminescence microscopy of FDG uptake in an engineered 3D tumor-stoma model

Khan

Kim

Yang

et al. 2021

Eur J Nucl Med Mol Imaging

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show abstract

“…Cancer cells in most tumors are glycolytic, characterized by a higher rate of glucose uptake compared to the normal surrounding tissue, even when su cient oxygen is present for oxidative glucose metabolism [1]. This phenomenon of aerobic glycolysis has led to the development and widespread use of 18 Fuorodeoxyglucose positron emission tomography (FDG-PET) for tumor imaging, which has been shown to signi cantly improve the diagnosis, staging, and subsequent treatment of cancers. However, the spatial resolution of positron emission tomography (PET), which is in the range of 4-8 mm [2], creates a bottleneck for its application to complex and heterogeneous targets.…”

Section: Introductionmentioning

confidence: 99%

High-Resolution Radioluminescence Microscopy of FDG Uptake in an Engineered 3D Tumor-Stoma Model

Khan

Kim

Yang

et al. 2021

Preprint

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PURPOSEThe increased glucose metabolism of cancer cells is the basis for 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). However, due to its coarse image resolution, PET is unable to resolve the metabolic role of cancer-associated stroma, which often influences the metabolic reprogramming of a tumor. This study investigates the use of radioluminescence microscopy for imaging FDG uptake in engineered 3D tumor models with high resolution.METHODMulticellular tumor spheroids (A549 lung adenocarcinoma) were co-cultured with GFP-expressing human umbilical vein endothelial cells (HUVECs) within an artificial extracellular matrix to mimic a tumor and its surrounding stroma. The tumor model was constructed as a 200 µm-thin 3D layer over a transparent CdWO4 scintillator plate to allow high-resolution imaging of the cultured cells. After incubation with FDG, the radioluminescence signal was collected by a highly sensitive widefield microscope. Fluorescence microscopy was performed using the same instrument to localize endothelial and tumor cells.RESULTSSimultaneous and co-localized brightfield, fluorescence and radioluminescence imaging provided high-resolution information on the distribution of FDG in the engineered tissue. The microvascular stromal compartment as a whole took up a large fraction of the FDG, comparable to the uptake of the tumor spheroids. In vitro gamma counting confirmed that A549 and HUVEC cells were both highly glycolytic with rapid FDG-uptake kinetics. Despite the relative thickness of the tissue constructs, an average spatial resolution of 64 ± 4 µm was achieved for imaging FDG.CONCLUSIONOur study demonstrates the feasibility of imaging the distribution of FDG uptake in engineered in vitro tumor models. With its high spatial resolution, the method can separately resolve tumor and stromal components. The approach could be extended to more advanced engineered cancer models but also to surgical tissue slices and tumor biopsies.

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High-resolution beta imaging

Barthe¹,

Maitrejean²,

Carvou³

et al. 2020

Handbook of Radioactivity Analysis: Volume 2

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Technical Note: Scintillation well counters and particle counting digital autoradiography devices can be used to detect activities associated with genomic profiling adequacy of biopsy specimens obtained after a low activity ¹⁸F‐FDG injection

Abstract: Scintillation well counter measurements and CCD-based autoradiography have adequate sensitivity to detect the tumor burden needed for genomic profiling during F-FDG PET/CT-guided 18G core needle biopsies of liver adenocarcinoma metastases.

Cited by 9 publications

References 31 publications

High-resolution radioluminescence microscopy of FDG uptake in an engineered 3D tumor-stoma model

High-resolution radioluminescence microscopy of FDG uptake in an engineered 3D tumor-stoma model

High-Resolution Radioluminescence Microscopy of FDG Uptake in an Engineered 3D Tumor-Stoma Model

High-resolution beta imaging

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Technical Note: Scintillation well counters and particle counting digital autoradiography devices can be used to detect activities associated with genomic profiling adequacy of biopsy specimens obtained after a low activity 18F‐FDG injection

Abstract: Scintillation well counter measurements and CCD-based autoradiography have adequate sensitivity to detect the tumor burden needed for genomic profiling during F-FDG PET/CT-guided 18G core needle biopsies of liver adenocarcinoma metastases.

Cited by 9 publications

References 31 publications

High-resolution radioluminescence microscopy of FDG uptake in an engineered 3D tumor-stoma model

High-resolution radioluminescence microscopy of FDG uptake in an engineered 3D tumor-stoma model

High-Resolution Radioluminescence Microscopy of FDG Uptake in an Engineered 3D Tumor-Stoma Model

High-resolution beta imaging

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Technical Note: Scintillation well counters and particle counting digital autoradiography devices can be used to detect activities associated with genomic profiling adequacy of biopsy specimens obtained after a low activity ¹⁸F‐FDG injection