A New Multimodal Molecular Imaging Approach to Guide Intra-Operative Tumor Resection and Post-Operative Treatment Planning

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Project Summary The first line of treatment for several cancer patients is surgical debulking which can suffer from poor tumor localization resulting in lengthy incomplete surgeries and repeat visits. Our objective is to provide physicians with an entirely new multimodal molecular imaging strategy that has the potential to offer 1) intra-operative surgical guidance to ensure complete resection of the tumor, and 2) post-operative molecular expression information to improve therapeutic decision-making. Oral squamous cell carcinoma (OSCC) is an ideal cancer on which to develop our new multimodal imaging approach as it suffers from poor tumor demarcation and is easy to access with optical imaging tools. We intend to develop an entirely new class of multimodal nanoparticles (NPs) to serve as our tumor targeting contrast agents. These new NPs are intended to provide real-time fluorescence image guidance during tumor resection and Raman multiplexed imaging to identify molecular expression and drug target availability for effective therapy. These multimodal NPs have the potential to provide physicians with a molecular map of the tumor with improved sensitivity and specificity not previously achievable with existing single mode molecular imaging technologies. Ongoing attempts toward developing new contrast agents have faced major problems in gaining regulatory approval. Our innovative approach utilizes the dyes that are already FDA approved for the coloring of our foods, drugs and cosmetics. Color is all around us, however, we often take for granted the sources of the vibrant colors we enjoy in our favorite candy, cosmetics and clothing. After curiously considering that these “colorful” organic dyes could offer more than just aesthetics, we recently discovered that they in fact have a multitude of useful optical properties (e.g. absorbance, fluorescence, Raman scattering) that make them ideal for imaging applications. We propose to integrate these dyes and their multimodal imaging capabilities into a nanoparticle construct specially designed to provide useful imaging contrast that enables improved cancer detection, localization and molecular profiling. We will begin our study by characterizing the physical characteristics of these newly fabricated NPs and their multimodal imaging capabilities. This will include in-vivo evaluation of their biodistribution and extravasation properties by utilizing multiple molecular imaging tools. We will then test their tumor targeting efficiency in cell culture and on human tissue. Our nanoparticles will actively target tumors through chemically conjugated targeting ligands and/or passively target the tumor through the enhanced permeability and retention effect. We will assess the tumor targeting efficiency and surgical navigation potential of our newly developed NPs with pre-existing preclinical and clinical molecular imaging tools. These studies will enable the repurposing of these aesthetically pleasing household organic dyes as multimodal imaging probes to enable an entirely new, and clinically translatable, paradigm. The images generated from these multimodal nanoparticles could improve cancer detection and localization for improved surgical resection, but also aid clinicians in the design of treatment protocols which are most suitable for the individual patient.