PoC - Physics of Cancer - Annual Symposium
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Poster, Friday, 19:00  
Tumor interstitial fluid pressure: a biophysical barrier hampering the uptake of macromolecular therapeutics

M. Hofmann1,2, E. McCormack3, R. Pflanzer1, J. Bereiter-Hahn4, H. Wiig2, S. Kippenberger1
 
1
 Department of Dermatology, Venereology, and Allergology, Goethe University, 60590 Frankfurt/Main, Germany
2
 Department of Biomedicine, University of Bergen, 5009 Bergen, Norway
3
 Department of Haematology, University of Bergen, 5009 Bergen, Norway
4
 Department of Cell Biology and Neurosciences, Goethe-University, 60439 Frankfurt/Main, Germany

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Elevated tumor interstitial fluid pressure (TIFP) is a characteristic of most solid tumors. Clinically, TIFP may hamper the uptake of drugs into tumor tissue reducing their therapeutic efficacy. In this study a means of modulating TIFP to increase the concentration of macromolecules into tumor tissue is presented, which is based on the rationale that elevated plasma colloid osmotic pressure (COP) pulls water from tumor interstitium lowering TIFP.
Concentrated human serum albumin (20%; HSA) reduced the TIFP time-dependently in xenograft models bearing human A431 carcinomas. TIFP was measured directly in the central region of solid tumors. To evaluate whether this reduction facilitates the uptake of macromolecules, distribution of fluorescently conjugated dextrans and cetuximab was probed employing novel time-domain near-infrared fluorescence imaging.
Co-administration of 20% HSA together with dextrans or cetuximab was found to lower the TIFP significantly and increase the concentration of the substances within the tumor tissue compared to controls.
These data demonstrate that increased COP lowers the TIFP within hours and increases the uptake of substances into the tumor interstitium, representing a novel approach to facilitate the delivery of therapeutics into tumor tissue.
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