A new three-dimensional ultrasound microimaging technology for preclinical studies using a transgenic prostate cancer mouse model.

Prostate cancer is the most common cancer in adult men in North America. Preclinical studies of prostate cancer employ genetically engineered mouse models, because prostate cancer does not occur naturally in rodents. Widespread application of these models has been limited because autopsy was the only reliable method to evaluate treatment efficacy in longitudinal studies. This article reports the first use of three-dimensional ultrasound microimaging for measuring tumor progression in a genetically engineered mouse model, the 94-amino acid prostate secretory protein gene-directed transgenic prostate cancer model. Qualitative comparisons of three-dimensional ultrasound images with serial histology sections of prostate tumors show 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 done in vivo with three-dimensional ultrasound and at autopsy was 0.998. Prospective tumor detection sensitivity and specificity were both >90% when diagnoses were based on repeated ultrasound examinations done 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. Compared with other microimaging and molecular imaging modalities, the application of three-dimensional ultrasound imaging to prostate cancer in mice showed advantages, such as high spatial resolution and contrast in soft tissue, fast and uncomplicated protocols, and portable and economical equipment that will likely enable ultrasound to become a new microimaging modality for mouse preclinical trial studies.

[1]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[2]  N. Greenberg,et al.  Autochthonous mouse models for prostate cancer: past, present and future. , 2001, Seminars in cancer biology.

[3]  M Van Glabbeke,et al.  New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. , 2000, Journal of the National Cancer Institute.

[4]  B. Klaunberg,et al.  Considerations for Setting up a Small-Animal Imaging Facility , 2004, Lab animal.

[5]  Xiaoming Xie,et al.  The EZC-prostate model: noninvasive prostate imaging in living mice. , 2004, Molecular endocrinology.

[6]  L From,et al.  Ultrasound backscatter microscope analysis of mouse melanoma progression. , 1996, Ultrasound in medicine & biology.

[7]  Guojun Wu,et al.  A novel knock-in prostate cancer model demonstrates biology similar to that of human prostate cancer and suitable for preclinical studies. , 2005, Molecular therapy : the journal of the American Society of Gene Therapy.

[8]  R. Weissleder.  Scaling down imaging: molecular mapping of cancer in mice , 2002, Nature Reviews Cancer.

[9]  P. Chaurand,et al.  A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential. , 2001, Cancer research.

[10]  T. Nelson,et al.  Three-dimensional ultrasound imaging. , 1998, Ultrasound in medicine & biology.

[11]  E. Chérin,et al.  A new ultrasound instrument for in vivo microimaging of mice. , 2002, Ultrasound in medicine & biology.

[12]  K. Pienta,et al.  Longitudinal cohort analysis of lethal prostate cancer progression in transgenic mice. , 1998, The Journal of urology.

[13]  R. Matusik,et al.  Prostate cancer in a transgenic mouse. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[14]  David E Goertz,et al.  High-frequency Doppler ultrasound monitors the effects of antivascular therapy on tumor blood flow. , 2002, Cancer research.

[15]  M. van Glabbeke,et al.  New guidelines to evaluate the response to treatment in solid tumors , 2000, Journal of the National Cancer Institute.

[16]  S. Gambhir,et al.  Visualization of advanced human prostate cancer lesions in living mice by a targeted gene transfer vector and optical imaging , 2002, Nature Medicine.

[17]  Anton Berns,et al.  The generation of a conditional reporter that enables bioluminescence imaging of Cre/loxP-dependent tumorigenesis in mice. , 2003, Cancer research.

[18]  A. Needles,et al.  High frequency nonlinear B-scan imaging of microbubble contrast agents , 2005, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[19]  J. Chin,et al.  Prostate targeting: PSP94 gene promoter/enhancer region directed prostate tissue-specific expression in a transgenic mouse prostate cancer model , 2002, Gene Therapy.

[20]  M. Shen,et al.  Mouse models of prostate carcinogenesis. , 2002, Trends in genetics : TIG.

[21]  S. Shapiro,et al.  An Analysis of Variance Test for Normality (Complete Samples) , 1965 .

[22]  M. Moussa,et al.  Knockin of SV40 Tag oncogene in a mouse adenocarcinoma of the prostate model demonstrates advantageous features over the transgenic model , 2005, Oncogene.

[23]  References , 1971 .

[24]  D. A. Christopher,et al.  Advances in ultrasound biomicroscopy. , 2000, Ultrasound in medicine & biology.