Value of ³¹P NMR spectroscopy in predicting the response of a xenografted human hypopharynx carcinoma to irradiation

Abstract

Purpose: An early indicator of tumor sensitivity to irradiation could provide useful information on the effectiveness of therapy and may facilitate more individual designs of treatment protocols. The aim of the present study was to evaluate the potential of in vivo ³¹P nuclear magnetic resonance spectroscopy in predicting the response of a xenografted human hypopharynx carcinoma to radiotherapy. Methods: The tumor had been serially heterotransplanted to athymic mice. ³¹P NMR spectra were collected before and at four intervals (24, 48, 72, and 120 h) after irradiation with 15 Gy or 30 Gy. Alterations of phosphorus metabolism were compared with the growth delays, the histological appearance, and the mitotic activity of the treated tumors. Results: Radiation with 30 Gy induced increases of the phosphodiester level (P < 0.001) as well as of the tumor pH (P < 0.05) and decreases of the phosphomonoester level (P < 0.001) within 48 h. The changes clearly preceded measurable tumor responses and were accompanied by severe histological destruction and marked depression of mitotic indices. However, none of these spectral alterations was significantly correlated with individual delays of tumor growth. The only parameters allowing a prediction of radiation-induced tumor responses were the pre-treatment levels of phosphomonoesters and -diesters. The ³¹P NMR spectroscopic changes observed after therapy with 15 Gy were either unsystematic or insignificant. Conclusions: Pre-treatment levels of tumor phospholipids were indicative of radiosensitivity in the xenografted human hypopharynx carcinoma investigated here. However, since phosphorus metabolism varies considerably among different tumor lines, it seems unlikely that there exists a uniform ³¹P NMR spectroscopic parameter predicting tumor response to radiation therapy.