In Fig. 2A, cumulative tumor uptake of 89Zr-MEHD7945A was observed in the AsPC-1 xenograft with 3.98 ± 0.21 percent injected dose per gram of tissue (%ID/g) at 24 h post-injection (p.i.) with the maximum tumor-bound activity achieved at 72 h p.i. at 6.18 ± 1.0%ID/g. Retention of the radiotracer was observed to as far as 96 h p.i. (6.23 ± 1.35%ID/g). AsPC-1 tumors imaged with the non-specific isotype 89Zr-IgG had significantly less uptake (0.62 ± 0.53%ID/g at 24 h, 0.80 ± 0.44%ID/g at 48 h, 1.03 ± 0.55%ID/g at 72 h, and 0.83 ± 0.29%ID/g, p < 0.001) at all time points (Fig. 2B). Higher cumulative tumor uptake was observed in BxPC-3 xenografts with 6.72 ± 1.40%ID/g at 24 h p.i. (Fig. 2C). The tumor uptake peaked at 8.91 ± 2.1%ID/g at 72 h with observed retention at 96 h p.i. (8.56 ± 2.3%ID/g). Separate BxPC-3 tumors imaged with 89Zr-IgG showed significantly less uptake (for example, 0.75 ± 0.32%ID/g at 24 h p.i, 0.65 ± 0.46%ID/g at 48 h p.i. p < 0.001, Fig. 2D) for all time points.Figure 2In vivo PET imaging. In AsPC-1 xenografts, tumor volumes-of-interest (VOI) expressed as % ID/g generated from the 89Zr-MEHD7945A PET scans exhibited uptake as early as 24 h p.i., peaking at 72 h p.i. and retained to as long as 96 h p.i. (A) 89Zr-IgG control PET scans showed minimal uptake within the tumor at all time points. (B) Similarly in BxPC-3 tumors, PET scans exhibited uptake at 24 h p.i. with a peak at 72 h p.i. (C) Non-specific tumor uptake using 89Zr-IgG in BxPC-3 xenografts showed nominal accumulation across all time points. (D) Whole body tissue distribution revealed high tumor tissue uptake of the tracer at 24 h p.i,, which plateaued at 48 h through 120 h p.i. in BxPC-3 xenografts. A competitive blocking study using unmodified MEHD7945A at 48 h p.i. displayed at least a two-fold decrease in tumor binding, indicative of the probe’s specificity. (E) Of note, normal pancreas demonstrated minimal non-specific binding on all time points, suggesting that an excellent signal-to-noise contrast can be achieved.