Prostate cancer (CaP) is the most common cancer in adult men in North America. Preclinical studies of prostate cancer employ genetically engineered (GE) mouse models because prostate cancer does not occur naturally in rodents. Widespread application of these models has been limited by the stochastic and often invisible nature of GE murine prostate tumors, which has complicated longitudinal studies by requiring large cohorts since autopsy was the only reliable method to evaluate treatment efficacy. This paper reports the first use of high-resolution three-dimensional (3-D) ultrasound micro-imaging to monitor prostate tumor development in GE mice. Qualitative comparisons of 3-D ultrasound images with serial histology sections of prostate tumors demonstrate the ability of ultrasound to accurately depict the size and shape of malignant masses in live mice. Ultrasound imaging identified tumors ranging from 2.4 to 14 mm maximum diameter. The correlation coefficient of tumor diameter measurements performed in vivo with 3-D ultrasound and at autopsy was 0.998. Prospective tumor detection sensitivity and specificity were both greater than 90% when diagnoses were based on repeated ultrasound examinations performed on separate days. Representative exponential growth curves constructed via longitudinal ultrasound imaging indicated volume doubling times of 5 and 13 days for two prostate tumors during an initial period of rapid progression. In conclusion, as compared with other micro- and molecular imaging modalities, the application of 3-D ultrasound imaging facility to small mouse CaP mice demonstrated advantages, such as high spatial resolution and contrast in soft tissue; fast and easy protocols, portable and economical, it will likely become the micro-imaging modality most readily adopted for mouse pre-clinical trial studies.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]