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Fig. 3. Heterogeneous distribution of trastuzumab through whole tumors. Tumors grown to 8 to 10 mm in diameter were dosed with 20 mg/kg trastuzumab and harvested at 3 h (A) or 26 h (B); 10 μm thick transverse sections were obtained at 1mm intervals from the tumor edge, were imaged for perfusion marker DioC7(3) (cyan), and stained for bound trastuzumab (red) and CD31 (dark blue). Examples of vessels with very little or no extravasating trastuzumab are illustrated (green arrows). Those sections obtained closer to the gross tumor edge of both the 3 h (A, left) and 26 h (B, left) show a greater proportion of tissue stained for trastuzumab than the more heterogeneous central sections (A and B, right). Quantitative analysis shows percentage of pixels positive for trastuzumab in sections at increasing distances from the tumor edge (C, left). The microregional distribution of trastuzumab as a function of distance from vasculature was analyzed on sections obtained 1 mm from tumor edge and compared with those at 4 mm; data is shown for tumors harvested at 3 h (C, middle) and 26 h (C, right) after treatment.
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