We tested the hypothesis that macromolecular agents will have a greater sensitivity in identifying areas of high regional mammary tumor permeability-surface area products than low molecular weight agents. New modalities such as ultrasound, MRI, and nuclear medicine may improve breast cancer diagnosis(1). MRI can detect small tumors, 1 mm, with nearly 100% sensitivity(2) and can differentiate benign from malignant tumors with an accuracy of only 30 to 40%(3). A need exists for more accurately characterizing tumor specificity with MR mammography. Dynamic contrast enhanced MR mammography shows promise, and is based on differences in capillary density. Only a subset of tumor cells acquire angiogenic activity and this results in heterogeneous capillary density and surface area(4). High regional capillary density indicates poor prognosis(5). Tumor secreted factors induce angiogenesis, including vascular endothelial growth factor (VEGF), which is necessary for metastasis and regions high in VEGF exhibit hyperpermeability(6). Some of the physiological byproducts of angiogenesis regulate the extraction of an agent by a tumor from the blood. This extraction depends on (a) capillary surface area, S, (b) capillary permeability, P, (c) capillary blood flow, F, (d) transit time of the agent through the tumor interstitium, and (e) the plasma half-life, T1/2 DIST(7, 8). By imaging the time evolution of a contrast agent in the lesion, one can model agent extraction. Knowing the plasma half-life of an agent and regional blood flow provides a measure of the capillary surface area and permeability. Such knowledge may provide a means of differentiating benign from malignant tumors.
We tested the hypothesis that macromolecular agents will have a greater sensitivity in identifying areas of high regional mammary tumor permeability-surface area products than low molecular weight agents. New modalities such as ultrasound, MRI, and nuclear medicine may improve breast cancer diagnosis(1). MRI can detect small tumors, 1 mm, with nearly 100% sensitivity(2) and can differentiate benign from malignant tumors with an accuracy of only 30 to 40%(3). A need exists for more accurately characterizing tumor specificity with MR mammography. Dynamic contrast enhanced MR mammography shows promise, and is based on differences in capillary density. Only a subset of tumor cells acquire angiogenic activity and this results in heterogeneous capillary density and surface area(4). High regional capillary density indicates poor prognosis(5). Tumor secreted factors induce angiogenesis, including vascular endothelial growth factor (VEGF), which is necessary for metastasis and regions high in VEGF exhibit hyperpermeability(6). Some of the physiological byproducts of angiogenesis regulate the extraction of an agent by a tumor from the blood. This extraction depends on (a) capillary surface area, S, (b) capillary permeability, P, (c) capillary blood flow, F, (d) transit time of the agent through the tumor interstitium, and (e) the plasma half-life, T1/2 DIST(7, 8). By imaging the time evolution of a contrast agent in the lesion, one can model agent extraction. Knowing the plasma half-life of an agent and regional blood flow provides a measure of the capillary surface area and permeability. Such knowledge may provide a means of differentiating benign from malignant tumors.