This is a Competitive Revision application under Notice Number NOT-OD-09-058, with Notice Title """"""""NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications"""""""". It is for the existing Phase II SBIR grant """"""""Molecular Mammography of Her-2 Cancers using Gold Nanoparticles"""""""", R44CA124190. Cancer imaging is important for tumor detection, determination of prognosis and treatments, image guided surgery and irradiation, as well as for monitoring responses. Molecular imaging of specific targets could identify tumor types and enable selection of appropriate drugs. Although mammography is widely used and more rapid and with higher resolution compared to PET, SPECT, and MRI, there are currently no targeted mammography contrast agents. In this currently funded grant, we are developing molecular targeted agents for mammography and CT by a nanotechnology approach using gold nanoparticle conjugates for imaging breast cancers. Her 2/neu protein is being targeted by use of antibodies attached to biocompatible gold nanoparticles using a mouse model. This would then be useful for non-invasive in vivo detection of this mutation which occurs in about 30% of breast cancers that could then be beneficially treated with the monoclonal antibody Herceptin. High resolution mammography and CT imaging would improve the limited sampling of biopsies and provide more thorough detection of even small tumors and metastases. If successful, this technology could be applied to other tumors for early detection and biochemical typing for more effective individualized treatments. Progress so far has demonstrated and quantified targeting to Her2-positive tumors compared to Her2- negative ones. Definitive detection of tumors smaller than currently possible has been shown using our approach, which has the potential to enable earlier and specific detection of breast cancers, and ultimately achieve better patient outcomes. However, a potential problem has become apparent during this work that might hinder clinical translation: the large gold nanoparticles (15 nm) used do not clear the body well, and their use might be difficult to justify in screening asymptomatic patients. Poor clearance would hinder FDA approval. Therefore, we propose in this Competitive Revision to develop gold nanoparticles that have good clearance. Overcoming this remaining obstacle would put in place a completed technology attractive to investors and clear the way for commercialization and clinical application. This work will address the American Recovery and Reinvestment Act (ARRA) of 2009 objectives by: 7 accelerating commercialization of the technology in order to achieve a significant benefit for cancer patients (by overcoming remaining obstacle) 7 creating new jobs 7 increasing economic efficiency by spurring technological advances in science and health 7 leveraging this one-time supplement by establishing critical strategic partnerships and/or securing third- party investments (i.e., non-federal funding) that will be necessary to achieve long-term commercialization goals (making the technology saleable to investors)
A novel method using nanotechnology will be developed for improved non-invasive imaging and detection of breast cancer types by mammography and CT. This should not only enable better early detection of smaller tumors and metastases without painful biopsies, but identify tumor types so that specific drugs for the type can be administered. Such a need exists to detect Her2 breast cancers, which account for about 30% of breast cancers, where the specific drug Herceptin(R) is available and improves survival.
| Hainfeld, J F; O'Connor, M J; Dilmanian, F A et al. (2011) Micro-CT enables microlocalisation and quantification of Her2-targeted gold nanoparticles within tumour regions. Br J Radiol 84:526-33 |
| Joshi, V N; Mitra, D; England, M D et al. (2010) Large Covalently Linked Fluorescent and Gold Nanoparticle Immunoprobes. Microsc Microanal 16:966-967 |
