title: Optical imaging detection of microscopic mammary cancer in ErbB-2 transgenic mice through the DA364 probe binding αv β3 integrins.
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.
authors.affiliation: Molecular Biotechnology Center, University of Turin, Turin, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Conti
authors.forename: Stefania
authors.initials: S
authors.lastname: Lanzardo
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.forename: Monica
authors.initials: M
authors.lastname: Montone
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bolli
authors.forename: Chiara
authors.initials: C
authors.lastname: Brioschi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Maiocchi
authors.forename: Guido
authors.initials: G
authors.lastname: Forni
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
mesh_terms: D000818:Animals; D002232:Carbocyanines; D005260:Female; D005455:Fluorescent Antibody Technique; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010456:Peptides, Cyclic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D002232:Carbocyanines; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D018719:Erb-b2 Receptor Tyrosine Kinases; C571145:DA364