FIGURE 1.

(A) Schematic illustrating T-DM1 and statin dose administration in single-dose ADC regime. NCIN87 gastric xenografts were established in female nude mice (≥8 per group). Once tumors reached 200–300 mm³, intravenous T-DM1 administration at 5 mg/kg weekly (for 1 wk—single-treatment regime) was started on day 1. Lovastatin (4.15 mg/kg) was orally administered 12 h before and simultaneously with intravenous injection of T-DM1. [⁸⁹Zr]Zr-DFO-trastuzumab was intravenously administered on day 39, and PET images were collected at 41 d after treatment. Immediately after PET imaging, organs were harvested for ex vivo biodistribution. Tumors were excised at 43 d after initiating therapy and used for Western blot analyses. Schematic was created with Biorender.com. (B) Tumor volumes (mm³) measured across 60 d for control, T-DM1 single-treatment regime, and T-DM1/statin single-treatment regime. Mean ± SD for at least 8 mice is shown. ****P < 0.0001 based on 2-way repeated measures ANOVA. (C) Fold-change in NCIN87 tumor volume for T-DM1 or T-DM1/statin (1 wk of therapy, single-treatment regime) and for T-DM1 or T-DM1/statin (5 wk, multiple-treatment regime reported (21)). Fold-change between day 0 and day 60 is displayed as mean ± SD (n ≥ 8). ****P < 0.0001 based on 1-way ANOVA.