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An ex Vivo Model for the Study of Tumor Metabolism by Nuclear Magnetic Resonance: Characterization of the Phosphorus-31 Spectrum of the Isolated Perfused Morris Hepatoma 7777¹

Department of Nuclear Magnetic Resonance and Medical Spectroscopy, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [R. A. G., T. R. B.], and Department of Physiology/Radiology, Michigan State University, East Lansing, Michigan 48824 [R. A. M.]

We have developed an isolated perfused tumor model to study the metabolism of solid tumors by nuclear magnetic resonance spectroscopy. Morris hepatomas (7777) were implanted in the inguinal region of Buffalo rats, such that they developed an isolated blood supply. These tumors were perfused with a RBC perfusate, removed from the animal, and studied by ³¹P nuclear magnetic resonance spectroscopy. ATP levels, as determined from the spectra, were stable for as long as the tumors were maintained in the magnet (7 h) only if the perfusate contained inosine, adenosine, and insulin. The adenosine and inosine were also required for recovery from ischemia. Under these conditions, ischemia did not result in a change in tumor pH. The nucleoside triphosphate resonance was significantly larger than the ß nucleoside triphosphate resonance in spectra of some of the perfused tumors, suggesting that ADP above about 300 nmol/g wet weight was not complexed in these tumors. The adenylate levels determined from extracts, O₂ consumption, histology, and ³¹P nuclear magnetic resonance spectra of extracts of perfused tumors and tumors in situ were all similar, indicating the perfused tumor is a reasonable model of the tumor in vivo.

¹ Supported by NIH Grant CA4078.

² To whom requests for reprints should be addressed.

Received 3/14/90. Accepted 11/20/90.