Measurement of intratumor pH by pH indicator used in F-19-magnetic resonance spectroscopy - Measurement of extracellular pH decrease caused by hyperthermia combined with hydralazine

RATIONALE AND OBJECTIVES. Without affect of metabolic changes, the authors measured intratumor pH by using F-19-magnetic resonance spectroscopy (MRS) with a fluorine compound (ZK-150471) on the basis of a calibration curve by pH electrode. METHODS. Using the 4,7-tesla magnetic resonance apparatus, a fluorine compound that had acid-base equilibrial change and was impermeable within cell membranes was used. The fluorine compound was injected intravenously. The signal was obtained from mouse mammary cancer by creating an experimental tumor on the leg of mice. And the tumors, which were heated with and without hydralazine. The pH evaluated from chemical shift of the fluorine compound. The pH data was obtained from an electrode for reference. RESULTS. The pH of nontreated tumors (n = 25) were 6.94 + 0.091. The pH decreased to 6.772 + 0.169 at 20 minutes even after 20 minutes of heating, and decreased to <6.71 at 40 minutes after every heating time. The pH decreased to 6.456 at 20 minutes after 15 minutes of heating combined with hydralazine, and to 6.416 at 40 minutes after same treatment. CONCLUSIONS. It is possible to measure the extracellular pH by F-19-MRS with the fluorine compound noninvasively in vivo, even after heating.