Controlled radio-frequency hyperthermia using an MR scanner and simultaneous monitoring of temperature and therapy response by (1)H, (23)Na and (31)P magnetic resonance spectroscopy in subcutaneously implanted 9L-gliosarcoma.

A magnetic resonance (MR) technique is developed to produce controlled radio-frequency (RF) hyperthermia (HT) in subcutaneously-implanted 9L-gliosarcoma in Fisher rats using an MR scanner and its components; the scanner is also simultaneously used to monitor the tumour temperature and the metabolic response of the tumour to the therapy. The method uses the (1)H chemical shift of thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (TmDOTA(-)) to monitor temperature. The desired HT temperature is achieved and maintained using a feedback loop mechanism that uses a proportional-integral-derivative controller. The RF HT technique was able to heat the tumour from 33 degrees to 45 degrees C in approximately 10 min and was able to maintain the tumour temperature within +/-0.2 degrees C of the target temperature (45 degrees C). Simultaneous monitoring of the metabolic changes with RF HT showed increases in total tissue and intracellular Na(+) as measured by single-quantum and triple-quantum filtered (23)Na MR spectroscopy (MRS), respectively, and decreases in intra- and extracellular pH and cellular bioenergetics as measured by (31)P MRS. Monitoring of metabolic response in addition to the tumour temperature measurements may serve as a more reliable and early indicator of therapy response. In addition, such measurements during HT treatment will enhance our understanding of the tumour response mechanisms during HT, which may prove valuable in designing methods to improve therapeutic efficiency.