Application of “Image and Treat Paradigm” to non-invasive monitoring of HER2 Receptor Expression during Monoclonal Antibody Treatment of Breast Carcinomas.

With the advent of molecular medicine, neo-adjuvant drugs such as monoclonal antibodies are becoming treatment of choice for tumor cells over-expressing specific surface receptors. As a prominent example, amplification of the HER2/neu gene and/or its over-expression has been identified in 20–30% of invasive breast and other carcinomas such as ovarian carcinomas. The HER2-positive status is correlated with a poor prognosis. However, up to now, quantitative estimates of this important characteristic have been limited to ex vivo ELISA essays of tissue biopsies and/or PET-based analysis. We have developed a novel approach in optical imaging, involving specific probes that do not interfere with the binding of the therapeutic agents, thus, excluding competition between therapy and imaging. Affibody-based molecular probes seem to be ideal for in vivo analysis of HER2 receptors using near-infrared optical imaging. Subcutaneous tumor xenografts, expressing different levels of HER2 (BT474, MDA-MB361, MCF7, U251,), are imaged at different times post-injection. Mathematical modeling allowed assessment of correlation between measured characteristics and HER2 expression levels from ex-vivo assays of the same tumors.  These studies show that ourmathematical modeling of the temporal variations of fluorescent intensities can overcome the non-specific changes of fluorescent signals in order to quantify  the number of receptors which are a measure of treatment efficacy.