Optical imaging detection of microscopic mammary cancer in ErbBa??2 transgenic mice through the DA364 probe binding ?±v?23 integrins

摘要

Despite spontaneous tumor growth in genetically engineered mice being one of the most recognized tools for the in vivo evaluation of novel diagnostic and therapeutic anticancer compounds, monitoring early stage lesions in live animals is a goal that has yet to be achieved. A large number of targets for the molecular imaging of various diseases have been identified and many imaging technologies, including optical techniques are emerging. One of the most commonly exploited targets in tumor imaging is ?±v?23 integrin, which plays an important role in the expansion, invasiveness and metastatic capability of a number of cancers, including breast cancer. The aim of this study was to set up an optical imaging method for the early detection of autochthonous mammary cancer in female BALB/c mice transgenic for the rata??ErbBa??2 oncogene (BALBa??neuT). We show that DA364, a neara??infrared fluorescence argininea??glycinea??aspartic acid cyclic probe, was taken up by neoplastic mammary glands and that its uptake increased with cancer progression. By contrast, the nonaccumulation of DA364 in the healthy mammary glands of virgin and lactating wilda??type mice suggests that the probe specifically targets breast cancers. Comparisons of optical imaging with wholea??mount and histological findings showed that DA364 allows the noninvasive visualization of atypical hyperplasia and microscopic foci of in situ carcinoma 2a??months before mammary lesions become detectable by palpation. Moreover, DA364 was successfully used to monitor the outcome of anticancer vaccination. Therefore, it can be considered a promising early detection tool in neara??infrared noninvasive optical imaging for the early diagnosis of breast cancer. Copyright ?? 2013 John Wiley & Sons, Ltd.