Abstract P3-13-08: Preclinical validation of a new tumor imaging agent targeting αvβ3 to detect breast tumor using NIR-light imaging
Authors: F Beurrier, A Dutour, Y Chen, E Froc, P Gayet, S Guillermet, P Rizo, N Chopin, C Faure, MA Dammaco, S Klinger, D Ferraioli, G Garin, I Treilleux
Journal: Cancer Research (2017)

Abstract Surgery is still a essential step for breast cancer treatment. Complete tumor removal during surgery rely on surgeon's ability to differentiate tumor from normal tissue. To date, no intra operative method is available and reliable enough to help the surgeon delineate precisely tumor extension in the adjacent normal tissue. Thus, surgeons rely solely on pre operative imaging techniques to delineate tumor margins. Recent advances made in the field of non-invasive imaging and vectorized nano-size particles have revealed a remarkable potential for improved tumor-margin detection. AngiostampTM is a new fluorescent agent for intra operative imaging. This system provides strong binding on αvβ3 integrin-rich tumor neoangiogenesis. Our general hypothesis is that targeting αvβ3 integrin-rich breast carcinoma neoangiogenesis should provide improved delivery of diagnostic compounds and assist surgeons intra operatively using near-infrared imaging techniques. We conducted preclinical studies to evaluate the distribution of angiostampTM in vivo in murine breast tumor model and to determine the expression of αvβ3 integrin on human breast specimens. The capacity of AngiostampTM to target αvβ3 integrin was assessed in 4T1 breast tumor model. After tumor implantation, mices were injected with AngiostampTM or a saline solution. Detection of the tumors was performed at different timepoints (early, progressive and established tumors, N= 24 mices/timepoint) using near infrared (NIR) imaging system (FluobeamTM) to detect fluorescence in tumor tissue. In parallel, the expression of αvβ3 integrins in normal breast tissue, benign lesions (N=20) and various tumors subtypes (N=120) was assessed by immunohistochemistry. In mice injected with AngiostampTM, fluorescence was observed only within the tumors with low background. AngiostampTM labeled tumors at all timepoint. No false negative fluorescence was found as confirmed by histopathological analyses. In humans, the αvβ3 integrin are expressed in normal breast epithelial cells and benign metaplastic or proliferative epithelial lesions. However, due to the density of carcinomatous cells, the level of expression was much higher in breast cancer: 94% of invasive ductal carcinomas and 100% of invasive lobular carcinomas had a membranous staining (moderate to high intensity). Expression in breast cancer was not restricted to tumor subtypes neither hormone receptor expression nor SBR grade. Based on this preclinical demonstration, AngiostampTM could allow a better intra-operative detection of tumor bed in breast cancer, increasing the efficiency of surgical procedure especially for infraclinic disease and decreasing the rate of second surgery. Preclinical development is ongoing and the first clinical trial is expected in 2017. Citation Format: Beurrier F, Dutour A, Chen Y, Froc E, Gayet P, Guillermet S, Rizo P, Chopin N, Faure C, Dammaco MA, Klinger S, Ferraioli D, Garin G, Treilleux I. Preclinical validation of a new tumor imaging agent targeting αvβ3 to detect breast tumor using NIR-light imaging [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-13-08.