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Time domain optical imaging validates uptake of therapeutic macromolecules after lowering of tumor interstital fluid pressure in a xenograft tumor model

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons83974

Hofmann,  M
Department Empirical Inference, Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Hofmann, M., McCormack E, Wiig, H., & Kippenberger, s. (2010). Time domain optical imaging validates uptake of therapeutic macromolecules after lowering of tumor interstital fluid pressure in a xenograft tumor model. Poster presented at 2010 World Molecular Imaging Congress (WMIC), Kyoto, Japan.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0013-BE8C-9
Abstract
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. 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 the usage of time-domain near-infrared fluorescence imaging to monitor the uptake of substances into the tumor interstitium to identify a novel approach of drug delivery of therapeutics into tumor tissue.