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Tumor Transport Physiology

Implications for Imaging and Imaging-Guided Therapy

¹ All authors: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions, 600 N. Wolfe St., Baltimore, MD 21287.

View larger version (96K): [in a new window]   Fig. 1. —Pie chart shows typical composition of solid tumors.

View larger version (75K): [in a new window]   Fig. 2A. —Illustrations depict basic steps involved in tumor angiogenesis. Normal capillary has intact endothelium.

View larger version (67K): [in a new window]   Fig. 2B. —Illustrations depict basic steps involved in tumor angiogenesis. Host capillaries dilate and develop increased permeability.

View larger version (96K): [in a new window]   Fig. 2C. —Illustrations depict basic steps involved in tumor angiogenesis. Fibrin leaks from blood pool into interstitium, creating extracellular matrix that facilitates cell growth. Proteases and collagenases break down capillary basement membranes.

View larger version (97K): [in a new window]   Fig. 2D. —Illustrations depict basic steps involved in tumor angiogenesis. Endothelial cells proliferate across disrupted basement membrane and canalize into functional vessel.

View larger version (71K): [in a new window]   Fig. 3. —Illustration of outer margin of tumor depicts abnormal and heterogeneous vascular supply in solid tumors. Tumor periphery (advancing front) typically has best vascular supply. Central portions of larger tumors are often hypovascular, with areas of hypoxia and central necrosis. Tumor vessels are abnormal in structure and function, with increased tortuosity and corkscrew configurations.

View larger version (78K): [in a new window]   Fig. 4A. —Illustrations show effect of interstitial pressure in tumor on transport of contrast agents and drugs across vessel wall into tumor interstitium. In normal tissues, intravascular pressure is much higher than interstitial pressure. Molecules are transported across vessel wall by convection process that is driven by pressure gradients.

View larger version (76K): [in a new window]   Fig. 4B. —Illustrations show effect of interstitial pressure in tumor on transport of contrast agents and drugs across vessel wall into tumor interstitium. High pressure in tumor interstitium minimizes convective (pressure gradient—driven) transfer of molecules out of vessels and to targeted tumor cells. Convective transfer is particularly important for large molecules, which move slowly by diffusion. Interstitial pressure is elevated almost uniformly throughout most of tumor. Pressure drops off at tumor periphery, resulting in a pressure gradient that drives molecules out of tumor by convection.

View larger version (75K): [in a new window]   Fig. 5. —Illustration shows barriers faced by molecule crossing interstitium to reach targeted cancer cell. Because transport in compartment is primarily by diffusion, large molecules move slowly. Molecular transport is further hindered by binding within interstitium, enzymatic destruction, and inactivation by acidic environment encountered in hypoperfused, hypoxia areas in center of tumor.

View larger version (97K): [in a new window]   Fig. 6. —67-year-old man with prostate cancer. SPECT image with radiolabeled antibodies shows poor signal-to-background contrast, which has generally limited usefulness of antibody-based imaging agents. Barriers that solid tumors present to delivery of tumor-specific but high-molecular-weight molecules, such as antibodies, can reduce effectiveness of such agents.

View larger version (181K): [in a new window]   Fig. 7. —47-year-old man with hepatocellular carcinoma. Arterial-phase helical CT scan reveals focal area of early enhancement (arrow) attributable to hepatocellular carcinoma. Such enhancement is related to neovascularity and increased capillary permeability in tumor. Both CT and MR arterial-phase imaging exploit process of tumor angiogenesis to reveal tumors.

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