1546P - Preclinical validation of a new tumor imaging agent targeting aVb3 to detect breast tumor using NIR-light imaging

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Translational Research
Presenter Frédéric Beurrier
Citation Annals of Oncology (2016) 27 (6): 526-544. 10.1093/annonc/mdw392
Authors F. Beurrier1, I. Treilleux2, Y. Chen3, E. Froc1, P. Gayet4, S. Guillermet4, P. Rizo4, N. Chopin1, C. Faure1, D. Dammaco1, S. Klinger1, D. Ferraioli1, G. Garin5, A. Dutour3
  • 1Surgical Oncolgoy, Centre Léon Bérard, 69008 Lyon - Lyon/FR
  • 2Biopathology Department, Centre Léon Bérard, Lyon/FR
  • 3Basic Research Center, Centre Léon Bérard, 69008 Lyon - Lyon/FR
  • 4Preclinical Development, Fluoptics, 38040 - Grenoble/FR
  • 5Clinical Research, Centre Léon Bérard, Lyon/FR

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

Frederic Beurrier

Funding

CAnceropole Rhone Alpes Auvergne

Disclosure

All authors have declared no conflicts of interest.