This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rofstad, E. K. Articles by Sutherland, R. M. Search for Related Content PubMed PubMed Citation Articles by Rofstad, E. K. Articles by Sutherland, R. M.

³¹P Nuclear Magnetic Resonance Spectroscopy Studies of Tumor Energy Metabolism and Its Relationship to Intracapillary Oxyhemoglobin Saturation Status and Tumor Hypoxia¹

Experimental Therapeutics Division and Departments of Radiation Oncology and Biophysics, University of Rochester Cancer Center, Rochester, New York 14642

Relationships between tumor bioenergetic status on the one hand and intracapillary oxyhemoglobin (HbO₂) saturation status and fraction of radiobiologically hypoxic cells on the other were studied using two murine sarcoma lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI). Tumor energy metabolism was studied in vivo by ³¹P nuclear magnetic resonance (NMR) spectroscopy and the resonance area ratio (PCr + NTPß)/P₁ was used as parameter for bioenergetic status. Intracapillary HbO₂ saturation status reflects the oxygen supply conditions in tumors and was measured in vitro using a cryospectrophotometric method.

The KHT, RIF-1, and MLS lines showed decreasing bioenergetic status, i.e., decreasing PCr and NTPß resonances and an increasing P₁ resonance, with increasing tumor volume, whereas the OWI line showed no changes in these resonances during tumor growth. The volumedependence of the HbO₂ saturation status differed similarly among the tumor lines; HbO₂ saturation status decreased with increasing tumor volume for the KHT, RIF-1, and MLS lines and was independent of tumor volume for the OWI line. Moreover, linear correlations were found between bioenergetic status and HbO₂ saturation status for individual tumors of the KHT, RIF-1, and MLS lines. These observations together indicated a direct relationship between ³¹P-NMR spectral parameters and tumor oxygen supply conditions. However, this relationship was not identical for the different tumor lines, suggesting that it was influenced by intrinsic properties of the tumor cells such as rate of respiration and ability to survive under hypoxia. Similarly, there was no correlation between bioenergetic status and fraction of radiobiologically hypoxic cells across the four tumor lines. This indicates that ³¹P-NMR spectroscopy data have to be supplemented with other data, e.g., rate of oxygen consumption, cell survival time under hypoxic stress, and/or fraction of metabolically active, nonclonogenic hypoxic cells, to be useful in quantitative determination of tumor hypoxia and hence prediction of tumor radioresistance caused by hypoxia.

¹ Financial support was received from The Norwegian Cancer Society, The Fulbright Program and Grants CA-20329 and CA-11198 from The National Cancer Institute.

² To whom requests for reprints should be addressed, at Department of Biophysics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo 3, Norway.

Received 2/ 4/88. Revised 5/18/88. Accepted 6/24/88.

This article has been cited by other articles:

				K. Maseide and E. K. Rofstad CCD imaging in cryospectrophotometric determination of microvascular oxyhemoglobin saturations Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2910 - H2918. [Abstract] [Full Text] [PDF]