P128	Characterization of functional and morphological properties of microcirculation in leukemic tumors in vivo.
1M.Schroeder, 1Chr.Schaefer, 1C.Joscheck, 2W.Fiedler, 1W.Rüther, 1N.Hansen-Algenstaedt
1Department of Orthopaedic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, DE; 2Department of Internal Medicine II, University Hospital Hamburg-Eppendorf, Hamburg, DE.

Introduction Functional properties of tumor vasculature are critical for the progression of tumors and for efficiency of tumor therapy. While angiogenesis and microvascular properties of solid tumors have been studied extensively, only little is known about the microcirculation of leukemic tumors. Therefore we established two mouse models allowing long-term observations of leukemic tumor growth and angiogenesis in vivo using intravital microscopy. Methods Megacarioblastic AML cells expressing Red-Fluorescence-Protein were implanted into severe combined immunodeficient mice using the cranial and femur window preparation. Intravital fluorescence microscopy was performed for quantitative measurements of vascular permeability (P), blood flow rate (BFR), leukocyte-endothelial-interaction (LEI), vessel density (VD), tissue-perfusion rate (TPR) and mean vessel diameter. Furthermore scanning-electron-microscopy and laser-scanning-microscopy were performed. Results Initial tumor growth was associated with a peak in P and VD. Both Parameters reached a steady state from day 37 to day 55. Reduction in VD was associated with a loss in capillaries while blood vessels with diameters above 12 ?m remained constant. Parameters determining tissue perfusion decreased until day 55 resulting in a 50% reduction in TPR. LEI was found to be increased without an increase in leukocyte extravasation. Microcirculation of Leukemic Tumor (Mo7e, RFP) in vivo. Bone Marrow (A,B) and Meningiosis leukemica Conclusion We report here the functional and morphological dynamics in leukemic tumor microcirculation from induction of angiogenesis until late stage disease. Tumor vascularization is not only spatially but also temporarily heterogeneous. The decrease of tissue perfusion due to the reduction of small vessels during tumor growth probably not only contributes to increased hypoxia but also to limited drug delivery. The temporarily changing microcirculatory properties imply the necessity of step-specific therapeutic strategies.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.