To date, complete tumor removal during surgery depends on surgeon's ability to differentiate tumor from normal tissue. AngioStampTM which binds αv�3 integrin is a new fluorescent agent for imaging during cancer surgery. It conscists of a cyclodecapeptide scaffold with 4 cyclic Arg-Gly-Asp (RGD) pentapeptide motifs on one side, and a fluorescent dye on the other side. We conducted preclinical studies to evaluate the distribution of AngioStampTM in vivo in mouse breast tumor model and to determine the expression of αv�3 integrin on human breast specimens.
The capacity of AngioStampTM to target αvß3 integrin was assessed in 4T1 breast tumor model. After tumor implantation, mices were injected with AngioStampTM or a saline solution (control group). Detection of the tumors was performed at different timepoints (early, progressive and established tumors, N= 24 mices/ timepoints) using near infrared (NIR) imaging system (FluobeamTM) to detect fluorescence in tumor tissue. In parallel, we evaluated the expression of αvß3 integrin in normal breast tissue, benign lesions (N = 20) and various tumors subtypes (N = 120) by immunohistochemistry.
In mice injected with AngioStampTM, fluorescence was observed only within the tumors with low background. AngioStampTM labeled tumors at all timepoints. No false negative fluorescence was found as confirmed by histopathological analyses. In humans, the αvß3 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 per-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.
Clinical trial identification
Legal entity responsible for the study
CAnceropole Rhone Alpes Auvergne
All authors have declared no conflicts of interest.