31P NMR spectroscopic and near infrared spectrophotometric studies of effects of anesthetics on in vivo RIF-1 tumors. Relationship to tumor radiosensitivity.

Mice with subcutaneous RIF-1 tumors were anesthetized with sodium pentobarbital (PB) or ketamine plus acepromazine (KA) before acquisition of in vivo 31P nuclear magnetic resonance (NMR) spectra from tumors. The area of the inorganic phosphate resonance was significantly greater (relative to phosphomonoesters or the alpha-phosphate resonance of nucleoside triphosphate) in spectra obtained under PB anesthesia, suggesting that the hypoxic fraction of the tumor increased following PB anesthesia. In vivo near-infrared laser spectroscopy directly demonstrated that tumor oxyhemoglobin was reduced by more than 20% following PB but was not significantly affected by KA. Total hemoglobin (tumor blood volume) was reduced by 11% following PB anesthesia, but was not significantly affected by KA. Tumor growth delay induced by gamma-irradiation was shorter when tumors were irradiated under PB anesthesia than when irradiated under KA, showing that PB anesthesia had a radioprotective effect. These studies demonstrate that both the 31P NMR and near infrared methods can detect metabolic or physiological changes associated with an increase in tumor radioresistance (i.e., an increase in the radiobiological hypoxic fraction).