Fig. 2.
Pharmacodynamic effects of PI3K inhibitor NVP-BKM120 on breast carcinomas in MMTV-CreBRCA1f/fp53+/− mice. Female virgin mice developed spontaneous breast cancers at ages 8–12 months. A. Representative 18FDG PET-CT scan images of a tumor-bearing mouse at baseline (image on the left) and within 48 hours of after start of treatments with the PI3K-inhibitor NVP-BKM120 (50 mg/kg/day by gavage, image on the right). This mouse had developed 4 simultaneous tumors. Arrows in red, green, yellow and white are used to identify different tumors upon baseline (left) and post-treatment (right) imaging. The color palette for uptake ranges from dark blue to bright yellow with increasing count intensity. The changes in 18FDG-uptake were determined as described in Materials and Methods. They were a decrease by 45% (tumor with red arrow), 64 % (tumor green arrow), 64% (tumor yellow arrow), 56% (tumor white arrow). B. Suppression of AKT-phosphorylation on S473 as a result of treatments with NVP-BKM120 in vivo. Tumor tissue was obtained via core needle biopsy before and after two weeks of treatments with NVP-BKM120, fixed and processed for IHC with anti-pAKT (S473) antibodies. For additional IHC images see Fig. S1. C. Decrease in FDG-uptake in 6 mammary carcinomas. Relative decrease in FDG-uptake was determined by the ratio of uptake at 48 hours (blue bars) or 2 weeks (red bars) to baseline. Tumor-specific FDG-uptake was determined as described in Materials and Methods. For additional PET-CT images see Fig. S2. D. Concordance of decrease in FDG-uptake and tumor shrinkage during a 2-week treatment with PI3K inhibitor NVP-BKM120. The tumor-bearing animal was imaged with FDG-PET (upper panel, tumor indicated with a yellow arrow before and after treatment, decrease in uptake 93%) and concomitant CT scan (lower panel) before (left) and while on treatment (right). The tumor is again marked in the CT scan with a yellow arrow in the axial and sagittal plane. The red outline indicates the tumor circumference before treatment to visualize treatment effect on tumor size.