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Role of Nuclear Magnetic Resonance Spectroscopy (MRS) in Cancer Diagnosis and Treatment: ³¹P, ²³Na, and ¹H MRS Studies of Three Models of Pancreatic Cancer¹

Department of Surgery A. Tel-Aviv Medical Center and School of Chemistry, Tel-Aviv University, 6 Weizmann Street, Tel-Aviv 64239, Israel

The role of nuclear magnetic resonance spectroscopy (MRS) in pancreatic cancer diagnosis and its treatment were assessed in three models of pancreatic neoplasms. Perfused MIA PaCa-2 human pancreatic cancer cells, s.c. implanted pancreatic tumors in hamsters, and pancreatic tumors induced in situ in rats by direct application of the carcinogen 7,12-dimethyl benzanthracene, were studied by phosphorous (³¹P), sodium (²³Na), and proton (¹H) MRS. ³¹P spectra of pancreatic cancer were qualitatively similar to those of intact organs. There were, however, variations in peak intensities and ratios. Phosphomonoester signals were prominent in both normal pancreases and tumors, but their levels depended on the proliferation rate and on environmental conditions. Thus, the phosphomonoester:ß-nucleoside triphosphate ratio was 1.15 ± 0.32 in 90% confluency and 1.31 ± 0.43 in 70% confluency, and this ratio increased upon lowering the perfusion rate. Total (intra- and extracellular) sodium concentrations, measured in the solid tumors, were 39–40 µmol/g wet weight in normal pancreases. Contrary to a previous hypothesis that malignant transformation is associated with increased sodium content, our ²³Na MRS data showed that there were no significant differences between pancreatic tumors and intact organs. Proton spectra of perchloric acid extracts revealed several differences between tumors and control pancreases. The principal findings were elevated levels of the amino acid taurine, from 1.17 ± 0.39 µmol/g wet weight in healthy pancreases, to 2.79 ± 0.71 µmol/g wet weight in pancreatic carcinoma in rats, and lactate levels that increased from 0.92 ± 0.2 to 6.19 ± 1.93 µmol/g wet weight, respectively. On the other hand, creatine and glutamate were higher in the normal pancreases. Pancreatic cancer is usually resistant to chemotherapy, and we evaluated the effects of the metabolic inhibitors 2-deoxyglucose and lonidamine on the human pancreatic cancer cells by MRS and cytotoxicity studies. The IC₅₀ of Adriamycin and 2-deoxyglucose were 1.49 ± 0.18 x 10⁶ and 136 ± 17 µg/ml, respectively. These results were similar to data obtained previously in multidrug-resistant human breast cancer cells, which were highly resistant (33-fold) to Adriamycin but were more susceptible (9-fold) to 2-deoxyglucose than their parental cells.

¹ This work was supported by a research grant from the Israel Cancer Association.

² To whom requests for reprints should be addressed.

Received 8/16/96. Accepted 2/22/97.