To understand the differences in tracer uptake between tumor models, spatial distribution of 89Zr-MEHD7945A was evaluated using digital autoradiography on AsPC-1 (Fig. 3A, left) and BxPC-3 tumors (Fig. 3A, right). Adjacent tumor sections of both AsPC-1 and BxPC-3 were evaluated for EGFR (Fig. 3B) and HER3 expression (Fig. 3C) by immunohistochemistry. Tissue viability and collagen content were qualitatively assessed via H&E staining (Supplementary Fig. S4A,B) and trichrome staining (Supplementary Fig. S4C), respectively. In both tumors, 89Zr-MEHD7945A accumulated in viable tumor regions with high EGFR expression (Fig. 3B). Staining of EGFR and HER3 showed strongest positivity on viable tumor cells. Although, the expression of EGFR in BxPC-3 and AsPC-1 tumor sections was similar, there was higher expression of HER3 in AsPC-1 when compared to BxPC-3. Areas with strong staining for HER3 co-localized with areas of high 89Zr-MEHD7945A registration (Fig. 3C). Taken together, the localization pattern indicates the dependence of 89Zr-MEHD7945A on both target expression and local pharmacokinetics. Collagen expression was qualitatively equivalent for both tumor sections. Looking at cell density, BxPC-3 tumors were observed to be two-fold more “cell dense” than AsPC-1 xenografts (258.8 ± 64.2 cells vs. 71.3 ± 14.9 cells, p = 0.0013, (Supplementary Fig. S4D).Figure 3Autoradiography and histology. Autoradiographs (A) of excised AsPC-1 (left) and BxPC-3 (right) tumor sections depicted co-localization of the tracer in areas where EGFR (BxPC-3 3+, AsPC-1 2+) (B) and HER3 (BxPC-3 1+, AsPC-1 2+) (C) are expressed.