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European Journal of Nuclear Medicine and Molecular Imaging

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01-10-2021 | Culture | Original Article

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

Authors: Syamantak Khan, Sungwoo Kim, Yunzhi Peter Yang, Guillem Pratx

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2021

Abstract

Purpose

The 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.

Method

Multicellular 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.

Results

Simultaneous 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.

Conclusion

Our 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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Title: High-resolution radioluminescence microscopy of FDG uptake in an engineered 3D tumor-stoma model
Authors: Syamantak Khan
Sungwoo Kim
Yunzhi Peter Yang
Guillem Pratx
Publication date: 01-10-2021
Publisher: Springer Berlin Heidelberg
Keywords: Culture
Positron Emission Tomography
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2021
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-021-05364-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Method

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Method

Results

Conclusion

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