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One-stop-shop tumor imaging: buy hypoxia, get lactate free
Ashley A. Manzoor, … , Thies Schroeder, Mark W. Dewhirst
Ashley A. Manzoor, … , Thies Schroeder, Mark W. Dewhirst
Published April 22, 2008
Citation Information: J Clin Invest. 2008;118(5):1616-1619. https://doi.org/10.1172/JCI35543.
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Commentary

One-stop-shop tumor imaging: buy hypoxia, get lactate free

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Abstract

The ability to noninvasively assess physiological changes in solid tumors is desired for its diagnostic and therapeutic potential. In this issue of JCI, Matsumoto and colleagues reveal their development and use of a novel imaging approach, combining pulsed electron paramagnetic resonance imaging (EPRI) with conventional MRI to image squamous cell carcinoma tumor–bearing mice (see the related article beginning on page 1965). This method provides coregistered images of oxygenation and blood volume/flow with the underlying anatomy and concentrations of metabolites such as lactate and choline. This technique, combining functional and anatomic imaging, shows immediate preclinical applicability in monitoring factors that control tumor hypoxia and metabolism and may have future clinical potential for monitoring tumor response to treatment.

Authors

Ashley A. Manzoor, Thies Schroeder, Mark W. Dewhirst

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Figure 1

Mechanisms underlying increased lactate concentrations in hypoxic and necrotic versus normoxic, well-perfused tumor areas.

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Mechanisms underlying increased lactate concentrations in hypoxic and ne...
Necrosis occurs within the hypoxic core of the (experimental) tumor. Lactate produced by perinecrotic, hypoxic cells is cleared through the microvasculature. Lacking a route of drainage, lactate accumulates in the necrotic cavity. In addition, hypoxia leads to an increase in baseline lactate production rate via the Pasteur effect (16). Consequently, the concentration of lactate in hypoxic tumor areas is determined by oncogenic/hypoxic lactate production, lactate backflow from necrosis, and other factors, such as vascular efficiency and substrate availability. The right panel illustrates these principles in a human cervical carcinoma (SiHa) xenografted in a mouse. The administered hypoxia marker pimonidazole (yellow) labels hypoxic cells, whereas external Hoechst 33342 (blue) marks better-perfused and oxygenated parts of the tumor. Lactate was determined from cryoslices using quantitative bioluminescence microscopy. The images were color encoded and coregistered with the pimonidazole/Hoechst image.
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