MICRO-ULTRASOUND IMAGING FOR BLADDER CANCER IN A MURINE MODEL

Abstract

4534 A validated mouse model for superficial bladder cancer is warranted to enable preclinical studies on intravesical anticancer agents. We sought to improve upon our previously described orthotopic superficial bladder cancer mouse model with validation using in vivo ultrasound imaging. Using the murine bladder tumor (MBT-2) cell line, 11 C3H/HeJ female mice were inoculated with 5 x 105 MBT-2 cells in 50 uL serum-free RPMI via transurethral catheterization without electrocautery. Using the VisualSonicsTM Vevo 770® ultrasound device, we performed transabdominal micro-ultrasound imaging 3, 6, and 15 days after tumor instillation. Imaging was also performed in all mice prior to tumor cell instillation. Tumors were measured using linear 2-dimensional measurements using sagittal and transverse imaging planes. Mouse bladders were subsequently harvested, formalin-fixed, embedded in paraffin, sectioned and stained with hematoxylin and eosin for confirmation of bladder tumors. Superficial bladder tumors were evident on micro-ultrasound imaging starting on day 3 post-MBT-2 cell instillation in all mice. Multifocal tumors were seen in 27% of mice on day 3, 91% on day 6, and 100% on day 15. Average number of tumors found on days 3, 6, and 15 was 1.3, 2.4, and 3.5. Mean tumor size (max dimension of largest tumor) on days 3, 6, and 15 was 0.7mm, 1.1mm, 1.3mm. Histology sections on all mice confirmed presence of bladder tumors in all mice. Using abdominal micro-ultrasound, we validate the presence of superficial bladder tumors in our MBT-2 mouse orthotopic bladder cancer model. Our model is reproducible and can be used to evaluate the efficacy of various intravesical anti-cancer agents. Tumors can be followed longitudinally for progression or regression with micro-ultrasound imaging.