Functionalized perfluorocarbon nanoemulsions for enhanced cell labeling for fluorine-19 MRI detection

This project aims to develop and commercialize a novel MRI probe technology for the cell therapy tools market. This project will transfer technology invented in the academic lab of Dr. Ahrens at UCSD, to Celsense, Inc., an established company that offers imaging agents for visualizing and quantifying the trafficking of cell therapies and inflammation in the body using magnetic resonance imaging (MRI). A common need for developers of cell therapies is a non-invasive means to visualize the biodistribution of cells following injection. Imaging of cell trafficking can provide crucial feedback regarding the persistence, optimal routes of delivery and therapeutic doses. This same information can also help to overcome regulatory barriers. Perfluorocarbon (PFC) nanoemulsion imaging agents are designed to be taken up by cells in culture, and following transfer to the subject, cells are detected in vivo using fluorine-19 (19F) MRI. The fluorine inside the cells yields cell- specific images, with no background signal. Images are readily quantified to measure apparent cell numbers at sites of accumulation. We and others have demonstrated that these methods can detect a wide range of cell types including various immune and stem cells. Previously, a collaboration between Celsense and the Ahrens lab has demonstrated the first clinical use of PFC 19F MRI technology to detect cellular immunotherapy in cancer patients. Looking forward, improving the sensitivity of 19F cell detection will lower the barriers for using this technology in a wider range of biomedical applications. Recent preclinical results from the Ahrens lab demonstrate enhanced cell detection sensitivity (andgt;8-fold) with 19F MRI via the invention of a new class of reagents combining PFC nanoemulsions with a surfactant containing a cell penetrating peptide from the transactivating transcription sequence (TAT) of the human immunodeficiency virus. The new “TAT-PFC” imaging probe technology will fit perfectly into Celsense’s reagent product line, particularly for the detection of lymphocytes and stem cells that are intrinsically challenging to label for imaging. The goal of this project is to perform academic-industry technology transfer to convert TAT-PFC into a commercial product, initially for the preclinical market. The Specific Aims of this project are: (1) Chemistry optimization and scale-up; (2) physical analytical characterization and stability testing of prototype nanoemulsion agent; (3) in vitro biological testing of cell uptake, cytotoxicity and cell phenotype in cells labeled with TAT-PFC; (4) generation of in vivo preclinical MRI datasets for product validation. Overall, Celsense generates revenue by international sales of its proprietary imaging agents for clinical and preclinical use, as well as specialized software, licensing fees, and fee-for-service contracts. Our view is that the new TAT-PFC imaging probe technology will be well-received by customers due to its enhanced sensitivity over existing cell detection products offered by the Company.This project aims to commercialize a novel magnetic resonance imaging (MRI) technology that is used to label and image therapeutic cells after they have been infused into the body. Therapeutic cells are currently being investigated to treat cancer and other life-threatening diseases. Imaging the therapeutic cells by MRI after they are placed in the body helps scientists and clinicians understand the best way to deliver the cells and how they behave afterwards. This new information can help speed the clinical development of cellular therapeutics.