Tissue gradients of energy metabolites mirror oxygen tension gradients in a rat mammary carcinoma model

Purpose: It has been shown that oxygen gradients exist in R3230AC tumors gr own in window chambers. The fascial surface is better oxygenated than the t umor surface. The purpose of the present study was to determine whether gra dients exist for energy metabolites and other end points related to oxygen transport. Methods and Materials: Imaging bioluminescence was used to measure ATP, glu cose, and lactate in cryosections of R3230AC tumors. Mean vessel density an d hypoxic tissue fraction were assessed using immunohistochemistry. Tumor r edox ratio was assessed by redox ratio scanning. Results: Lactate content and hypoxic fraction increased, whereas ATP, gluco se, redox ratio, and vessel density decreased from the fascial to the tumor surface. Conclusions: The data support a switch from aerobic to anaerobic metabolism concomitant with the PO, gradient. The vascular hypoxia that exists in per fused vessels at the tumor surface leads to macroscopic tissue regions with restricted oxygen availability and altered metabolic status. Methods to re duce tumor hypoxia may have to take this into account if such gradients exi st in human tumors. The results also have implications for hypoxia imaging, because macroscopic changes in PO2 (or related parameters) will be easier to see than PO2 gradients limited to the diffusion distance of oxygen. (C) 2001 Elsevier Science Inc.