Results: 4

1.
Figure 3

Figure 3. From: Dose Dependence of Intratumoral Perivascular Distribution of Monoclonal Antibodies.

(a) Experimentally observed perivascular antibody–antigen distribution ratio as a function of dose and (b) Krogh cylinder-based predicted perivascular distribution of extravasated antibody. The lower limit for signal in panel a was taken to be three standard deviations over the background signal. Equations and paramaters used to generate panel b are detailed in the Supplementary Data.

John J. Rhoden, et al. J Pharm Sci. 2012 February;101(2):860-867.
2.
Figure 2

Figure 2. From: Dose Dependence of Intratumoral Perivascular Distribution of Monoclonal Antibodies.

Selected images of tumor sections from xenografts in mice administered between 5 and 500 µg of anti-CEA antibody sm3e labeled with Alexa Fluor 488 24 h before sacrifice and tumor harvest. Blue pseudocolor represents DAPI; green pseudocolor represents sm3e; red pseudocolor represents blood vessels; not shown for clarity is antigen, which was also imaged in each section. Doses were 5, 15, 50, 150, and 500 µg in panels a–e, respectively. Note that low doses at 50 µg or less show clear perivascular distribution, whereas higher doses of 150 and 500 µg appear to show complete saturation of the tumor. All scale bars are 1 mm.

John J. Rhoden, et al. J Pharm Sci. 2012 February;101(2):860-867.
3.
Figure 4

Figure 4. From: Dose Dependence of Intratumoral Perivascular Distribution of Monoclonal Antibodies.

Plots of ϕ2 = 1 trendlines as a function of bolus dose IgG injected and the number of cell-surface antigens per tumor cell, allowing for the estimation of minimum doses required for tumor saturation. Data are plotted for a wide range of physiologically relevant antigen turnover rates. The shaded band represents a typical range of constitutive turnover half lives for membrane proteins. Parameters used in model calculations are given in Table 1. (a) 10 pM bivalent affinity and (b) 1 nM bivalent affinity.

John J. Rhoden, et al. J Pharm Sci. 2012 February;101(2):860-867.
4.
Figure 1

Figure 1. From: Dose Dependence of Intratumoral Perivascular Distribution of Monoclonal Antibodies.

(a) Depiction of an example of immunofluorescence image. Objects pseudocolored red indicate blood vessels, and green pseudocoloring represents extravasated antibody. Antibody was administered to the tumor-bearing mouse 24 h before euthanasia at a dose of 50 µg. Not shown for clarity are DAPI and antigen, both of which are also imaged with blood vessels and antibody. Scale bar, 1 mm. (b) Blood vessels have been thresholded and a Euclidean distance map applied to the thresholded vessels. Antigen-negative and necrotic regions of the tumor section can be manually removed from the analysis of this image. Pixel intensities are directly proportional to the distance from the nearest blood vessel. (c) Output of the automated MATLAB analysis of the antibody distribution from blood vessels. Antibody intensity values at large distances from the blood vessels are indistinguishable from those measured in tumors, which did not receive the antibody. Not shown for clarity is the corresponding antigen distribution.

John J. Rhoden, et al. J Pharm Sci. 2012 February;101(2):860-867.

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