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³¹P-Nuclear Magnetic Resonance Spectroscopy Studies of the Response of Rat Mammary Tumors to Endocrine Therapy¹

Cancer Research Campaign Biomedical Magnetic Resonance Research Group, Department of Biochemistry, and Ludwig Institute for Cancer Research, St. George's Hospital Medical School, London SW17 ORE, United Kingdom

We have used ³¹P-nuclear magnetic resonance spectroscopy to detect the metabolic changes that occur in estrogen-sensitive, N-methyl-N-nitrosourea-induced rat mammary tumors as they regress following ovariectomy. In untreated animals the spectra of the tumors showed a steady loss of high energy phosphates (phosphocreatine and nucleoside triphosphates) and an increase in inorganic phosphate. This was reversed after ovariectomy. Spectral changes occurred before detectable regression of the tumor. Estrogen-insensitive tumors, grown from implanted Rama 600 and 622 cells, did not regress in response to ovariectomy, and their high energy phosphates continued to fall; estrogen-sensitive tumors also failed to respond to sham ovariectomy. These effects are probably due to the reduction in cellular energy requirements that occurs when the hormonal stimulus to growth is removed. Because the nuclear magnetic resonance method is noninvasive, this technique should be applicable clinically as a means of predicting the response of a tumor to endocrine therapy.

¹ Supported by the Cancer Research Campaign, United Kingdom (L. M. R., A. N. S., M. S., J. R. G.).

² Present address: IGE Medical Systems, 260 Bath Road, Slough, Berkshire SL1 4ER, United Kingdom.

³ To whom requests for reprints should be addressed, at Cancer Research Campaign Biomedical Magnetic Resonance Research Group, Department of Biochemistry, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, United Kingdom.

Received 7/21/86. Revised 2/ 6/87. Revised 9/23/87. Accepted 9/30/87.