Value of 31 P 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 eectiveness 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 31 P 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. 31 P 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 signi®cantly 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 31 P NMR spectroscopic changes observed after therapy with 15 Gy were either unsystematic or insigni®cant. Conclusions: Pretreatment 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 31 P NMR spectroscopic parameter predicting tumor response to radiation therapy.Key words 31 P NMR spectroscopy á Hypopharynx carcinoma á Radiotherapy Abbreviations PCr phosphocreatine á PME phosphomonoesters á PDE phosphodiesters á P i inorganic phosphate á TPC total phosphorus content

Radiation effects on soluble metabolites in cultured HeLa cells examined by 1H MRS: Changes in concentration of glutathione and of lipid catabolites induced by gamma rays and proton beams

“…Nevertheless, the possibility of its detection with 1 H MRS seems important, as indicated by similar studies in the literature at high doses with 31 P MRS, a less sensitive technique [13,14,33,34].…”

“…As far as the lipid precursors are concerned, we want to explore their sensitivity in predicting the response to radiotherapy in cells, as this seems a subject of great concern in the field of radiation. Studies in the literature relate to the use of 31 P MRS [13,14,33,34]. In the present study, we aimed to exploit the higher sensitivity of 1 H MRS and the possibility, with this latter technique, of observing the choline signal.…”

High-field small animal magnetic resonance oncology studies

“…After 30 Gy single-dose RT, the PME/total phosphate ratio decreased while the PDE/total phosphate ratio increased (Jackel et al , 2000). Similarly, PME levels decreased, and GPC levels increased by 95 ± 15% in 4–7h, while β-ATP/Pi decreased by 25 ± 5% in subcutaneous murine Ehrlich ascites tumors after a single-dose of 10 Gy (Sharma and Jain, 2001).…”

“…Similarly, PME levels decreased, and GPC levels increased by 95 ± 15% in 4–7h, while β-ATP/Pi decreased by 25 ± 5% in subcutaneous murine Ehrlich ascites tumors after a single-dose of 10 Gy (Sharma and Jain, 2001). However, while tumoral pH increased after 30 Gy in the human hypopharynx carcinoma xenografts (Jackel et al , 2000), pH decreased after 10 Gy RT in the subcutaneous murine Ehrlich ascites tumors (Sharma and Jain, 2001). …”

Radiosensitivity of Rat Mammary Tumors Correlates With Early Vessel Changes Assessed by Power Doppler Sonography

“…Among other methods, nuclear magnetic resonance spectroscopy using phosphorus 31 seems to provide useful information and is being evaluated. 27 It has been shown that radiotherapy induces rapid changes in the membranes of endothelial cells, with increased vascular permeability, 28 but does not affect vascular density, as assessed by immunohistologic analysis within hours after irradiation. 29 However, in this study, radiation therapy was delivered as a single fraction of 18 Gy, which does not correspond to the usual modalities of radiotherapy in humans.…”