Abstract
Previous studies using MR spectroscopy have shown that the extracellular pH (pH~e~) of tumors is acidic compared to normal tissues. This has a number of important sequelae that favor the emergence of more aggressive and therapy‐resistant tumors. New MRI methods based on pH‐sensitive T~1~ relaxivity are an attractive alternative to previous spectroscopic methods, as they allow improvements in spatial and temporal resolution. Recently, pH‐dependent GdDOTA‐4AmP^5‐^ and a pH‐independent analog, GdDOTP^5‐^, were used to image renal pH in mice. The current study has used a similar approach to image pH~e~ in rat gliomas. Significant differences were observed compared to the renal study. First, the relaxivity of GdDOTP^5‐^ was found to be affected by the higher extracellular protein content of tumors. Second, the pixel‐by‐pixel analysis of the GdDOTP^5‐^ and GdDOTA‐4AmP^5‐^ pharmacokinetics showed significant dispersion, likely due to the temporal fluctuations in tumor perfusion. However, there was a robust correlation between the maximal enhancements produced by the two boluses. Therefore, to account for the local time‐courses differences, pH~e~ maps were calculated at the time of maximal enhancement in each pixel. Finally, the comparison of the pH~e~ and the time to maximal intensity maps revealed an inverse relationship between pH~e~ and tumor perfusion. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.