In vivo 19F NMR studies of hyperthermia: hydrophobic environments probed by halothane

The steady-state distribution of the general anesthetic halothane in different rat tissues, including a renal adenocarcinoma with and without hyperthermia treatment, has been evaluated by in vivo 19F NMR spectroscopy. The 19F spectra of halothane (which is a hydrophobic probe) from within tissue show differences in the partitioning between normal rat tissues and adenocarcinoma. Muscle, as a control tissue, exhibits a single large resonance around 0 ppm. However, the adenocarcinoma exhibits two slow-exchanging resonances separated by 0.3 ppm with the one at the more hydrophobic chemical shift being more sensitive to hyperthermia treatment. The results from this tumor model suggest that 19F NMR spectroscopy may be useful first in detecting a change in hydrophobic environments using a lipophilic probe such as halothane, and secondly in monitoring the effects of hyperthermia, a treatment whose effectiveness may involve changes at the level of the plasma membrane. Under conditions of continuous delivery, a resonance which is not detected in the spectra of halothane in excised tissue appears 5 ppm downfield from the resonance for halothane localized in tissues. A rotating frame experiment is used to show that this resonance is derived from anesthetic absorbed on the tissue surface.