Optical imaging detection of microscopic mammary cancer in ErbB-2 transgenic mice through the DA364 probe binding αv
Laura Conti1, Stefania Lanzardo, Manuela Iezzi
1Molecular Biotechnology Center, University of Turin, Turin, Italy.
Abstract:
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 αv β3 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 rat-ErbB-2 oncogene (BALB-neuT). We show that DA364, a near-infrared fluorescence arginine-glycine-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 wild-type mice suggests that the probe specifically targets breast cancers. Comparisons of optical imaging with whole-mount and histological findings showed that DA364 allows the noninvasive visualization of atypical hyperplasia and microscopic foci of in situ carcinoma 2 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 near-infrared noninvasive optical imaging for the early diagnosis of breast cancer.
Insights
This study introduces DA364, a near-infrared fluorescence probe, for early breast cancer detection in mice. It visualizes microscopic lesions noninvasively, enabling earlier diagnosis and monitoring of anticancer treatments.
Area of Science:
- Biomedical imaging
- Oncology
- Molecular diagnostics
Background:
- Early detection of mammary cancer is crucial for effective treatment.
- Current methods for monitoring spontaneous tumor growth in vivo have limitations.
- Alpha-v beta-3 (αv β3) integrin is a key target in breast cancer progression and metastasis.
Purpose of the Study:
- To develop an optical imaging method for early detection of autochthonous mammary cancer in mice.
- To evaluate the efficacy of a near-infrared fluorescence probe (DA364) for targeting αv β3 integrin in breast cancer.
- To assess the probe's ability to visualize early-stage neoplastic lesions noninvasively.
Main Methods:
- Utilized genetically engineered mice (BALB-neuT) with spontaneous mammary tumors.
- Administered DA364, an arginine-glycine-aspartic acid cyclic probe, for near-infrared fluorescence imaging.
- Compared optical imaging findings with whole-mount and histological analyses.
- Assessed probe uptake in neoplastic versus healthy mammary glands.
- Monitored the outcome of anticancer vaccination using DA364 imaging.
Main Results:
- DA364 was selectively taken up by neoplastic mammary glands, with uptake increasing with cancer progression.
- Healthy mammary glands showed minimal probe accumulation, indicating cancer specificity.
- Optical imaging with DA364 visualized atypical hyperplasia and microscopic carcinoma in situ 2 months before palpation.
- The probe successfully monitored the response to anticancer vaccination.
Conclusions:
- DA364 is a promising tool for early, noninvasive diagnosis of breast cancer using near-infrared optical imaging.
- This method allows visualization of pre-palpable mammary lesions.
- DA364 facilitates monitoring of therapeutic interventions like anticancer vaccination.
