One-stop-shop tumor imaging: buy hypoxia, get lactate free
J. Clin. Invest. Ashley A. Manzoor, et al. 118:1616 doi:10.1172/JCI35543 [
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Figure 1Mechanisms underlying increased lactate concentrations in hypoxic and necrotic versus normoxic, well-perfused tumor areas. 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.