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Effect of Estrogen Withdrawal on Energy-rich Phosphates and Prediction of Estrogen Dependence Monitored by in Vivo ³¹P Magnetic Resonance Spectroscopy of Four Human Breast Cancer Xenografts¹

The Finsen Center, National University Hospital [C. A. K., P. E. G. K., N. B.], Institute of Pathological Anatomy [C. A. K., P. E. G. K., M. S-T.], and NMR-Center [B. Q.], University of Copenhagen, Copenhagen, Denmark and Vincent Lombardi Cancer Research Center, Georgetown University Medical School, Washington, DC 20007 [R. C.]

The effect of estrogen withdrawal on energy metabolism was studied in four human breast cancer xenografts: the estrogen-dependent MCF-7 and ZR75-1 and the estrogen-independent ZR75/LCC-3 and MDA-MB-231. The tumors were grown in ovariectomized nude mice with a s.c. implanted estrogen pellet. After Gompertzian growth was verified, the estrogen pellet was removed from half of the animals. In vivo ³¹P magnetic resonance spectroscopy of the tumors was performed 1 day before and on days 2, 6, and 14 after estrogen removal. Estrogen withdrawal induced a significant increase in the nucleoside triphosphate:P_i ratio in the two estrogen-dependent xenografts, whereas this ratio remained unchanged in the estrogen-independent tumors. In ZR75/LCC-3 tumors a slight decrease in nuceloside triphosphate:P_i was observed following onset of estrogen stimulation after initial growth without estrogen. Extracts of freeze-clamped tumors prepared 14 days after estrogen removal were analyzed for ATP and phosphocreatine content. Our findings suggest a correlation between estrogen withdrawal and the steady-state concentrations of ATP, phosphocreatine, and P_i in human breast cancer xenografts. Discrimination analysis of the pretherapeutic spectra enabled us to identify the tumor line and the estrogen dependence of the tumors in 80–90% of all cases.

¹ This work was supported by grants from The Haensch Foundation, The Skovgaard Foundation, and The Danish Cancer Research Foundation.

² To whom requests for reprints should be addressed, at Department of Oncology ONK 5074, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.

Received 9/26/94. Accepted 2/16/95.

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