This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Leunig, M. Articles by Messmer, K. Search for Related Content PubMed PubMed Citation Articles by Leunig, M. Articles by Messmer, K.

Interstitial Fluid Pressure in Solid Tumors following Hyperthermia: Possible Correlation with Therapeutic Response¹

Institute Surgical Research, Ladwig-Maximilians-University of Munich, Klinikum Grosshadern, Marchioninistraße 15, 8000 Munich 70, Germany [M. L., A. E. G., M. D., G. Z., F. G., K. M.], and Steele Laboratory, Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114 [M. L., R. K. J.]

Elevated interstitial fluid pressure (IFP) of tumors may be a physiological barrier to the delivery of certain therapeutic agents. The objective of this study was to find out if IFP could be lowered using localized hyperthermia and if the reduction in IFP could predict the tumor response to treatment. Amelanotic melanoma (A-Mel-3) implanted into the dorsal skin of Syrian golden hamsters was exposed to hyperthermic treatment after 7 days of tumor growth at tumor volumes of about 100–150 mm³. Hyperthermia was induced by immersing the tumor in a water bath at 43°C for 30 or 60 min. Forty-eight h later the IFP of control and treated tumors was determined by using the wick-in-needle technique. The mean IFP in control tumors was 12.6 mmHg. Hyperthermic treatment for 30 min induced a significant decrease to 2.8 mmHg (P < 0.001 versus controls), whereas a 60-min immersion of the tumors induced a further decrease to 0.8 mmHg (P < 0.05 versus 43°C for 30 min). Separate experiments on tumor growth in corresponding groups of animals revealed a significant growth delay of 2.7 days after hyperthermia for 30 min. Enhanced growth delay and partial tumor response in 66% of the tumors were found following 60 min of hyperthermia at 43°C. The thermal dose-dependent decrease in IFP presumably results from the dose-dependent damage to the tumor vasculature. In addition, the association of an enhanced biological effect with a more pronounced reduction of interstitial fluid pressure suggests that the IFP might serve as a quantitative parameter to predict the response of tumors to hyperthermic therapy.

¹ Supported by a grant from the Bundesministerium für Forschung and Technologie (0706903A5) to A. E. G. and grants from the National Cancer Institute (CA37239 and CA49792) to R. K. J. M. L. is recipient of a Feodor-Lynen Fellowship (1991–1992), and R. K. J. was recipient of a Humboldt Senior Scientist Award (1990–1991).

² To whom reprint requests should be addressed.

Received 9/27/91. Accepted 11/20/91.

This article has been cited by other articles:

				M. Jain, G. Venkatraman, and S. K. Batra Optimization of Radioimmunotherapy of Solid Tumors: Biological Impediments and Their Modulation Clin. Cancer Res., March 1, 2007; 13(5): 1374 - 1382. [Abstract] [Full Text] [PDF]

				Y. Navalitloha, E. S. Schwartz, E. N. Groothuis, C. V. Allen, R. M. Levy, and D. R. Groothuis Therapeutic implications of tumor interstitial fluid pressure in subcutaneous RG-2 tumors Neuro Oncology, July 1, 2006; 8(3): 227 - 233. [Abstract] [Full Text] [PDF]

				M. J. Ali, Y. Navalitloha, M. W. Vavra, E. W.-Y. Kang, A. C. Itskovich, P. Molnar, R. M. Levy, and D. R. Groothuis Isolation of drug delivery from drug effect: Problems of optimizing drug delivery parameters Neuro Oncology, April 1, 2006; 8(2): 109 - 118. [Abstract] [Full Text] [PDF]

				G. Kong, R. D. Braun, and M. W. Dewhirst Characterization of the Effect of Hyperthermia on Nanoparticle Extravasation from Tumor Vasculature Cancer Res., April 1, 2001; 61(7): 3027 - 3032. [Abstract] [Full Text]