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Abstract Objective  The aim of this study was to compare a pure macromolecular contrast agent (Gd-DTPA-albumin) with a new protein-binding blood pool contrast agent (B22956/1) in terms of their capacity to investigate the microvasculature in an experimental model of mammary carcinoma. Materials and methods  Tumors were induced by subcutaneous injection of 5 × 105 BB1 cells into the backs of 5–7 week-old female FVB/neuNT233 mice. The animals were observed using DCE-MRI when the longest diameter of the tumor was 10.2±2.0 mm. DCE-MRI experiments were carried out using B22956/1 and (24 h later) Gd-DTPA-albumin. Results  DCE-MRI data showed that vasculature in the tumor rim was characterized by greater fractional plasma volume and transendothelial permeability than vasculature in the tumor core as measured by both contrast agents. Permeability to Gd-DTPA-albumin in the tumor core was hardly measurable while permeability to B22956/1 was substantial. Histologically the tumor core showed areas of well vascularized, viable tissue surrounded by necrotic regions. Conclusions  DCE-MRI experiments performed with B22956/1 are useful in the investigation of vasculature in those tumor regions that are characterized by low permeability to macromolecules. [ABSTRACT FROM AUTHOR]

Contrast-enhanced MRI, immunostaining and electron microscopy were used to detect areas of intense angiogenesis in experimental tumors. This work was also aimed at evaluating the possible effect of the surrounding tissues on tumor microvasculature and at studying the penetration of macromolecules in avascular areas. Human colon carcinoma cells were implanted in subcutaneous tissue of nude mice. Dynamic T1-weigthed 3D pulse sequences were acquired before and after administration of Gd-DTPA-albumin to obtain parametric maps of fractional plasma volume (fpv) and transendothelial permeability (Kps). The maps suggested that tumor can be subdivided into 4 zones located in the peripheral rim (zones I–II) or in the core (zones III–IV) of the tumor itself. Significant differences (p<0.001) were found in the values of Kps and fpv of zones I–II with respect to zones III–IV. In the peripheral rim, permeability was significantly higher (p<0.01) in the muscle-peripheral region (zone I) with respect to the skin-peripheral region (zone II). In areas with high Kps, histological and ultrastructural examination revealed clusters of newly formed vessels and signs of intense permeability. Numerous vascular vesicular organs were visible in these areas. In the tumoral core, analysis of the microcirculatory parameters revealed regions with mild permeability (zone III) and regions with negligible permeability (zone IV). These 2 zones were discriminated by the average value of Kps (p<0.05), while their fpv was not significantly different. Upon histological examination, the tumoral core exhibited necrotic areas; CD31 immunocytochemistry exhibited that it was diffusely hypovascularized with large avascular areas. Upon ultrastructural examination, capillaries were rarely visible and exhibited signs of endothelial cell damage. The results suggest that segmentation based on microvascular parameters detects in vivo zones characterized by immunocytochemical and ultrastructural aspects of intense angiogenesis. The finding that a certain amount of contrast agent penetrates in the tumoral core suggests that high oncotic and hydrostatic pressure only partially hinders the penetration of macromolecules. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]