NIH: Image-guided Drug Delivery [PAR-16-044]

This Funding Opportunity Announcement (FOA) will support innovative research in image-guided drug delivery (IGDD) for cancer and other diseases. The overarching goals of this FOA are to support the development of quantitative in vivo imaging methods for IGDD to guide, monitor, and evaluate drug delivery across different physical and physiological scales in order to interrogate biodistribution and target-drug interaction (pharmacokinetics and pharmacodynamics) and therapeutic response. Studies that are directed towards translation of IGDD technology to patient care are considered appropriate for this FOA.

Despite significant advancements against many types of cancer, neuro-, and cardiovascular diseases, challenging medical problems remain in each indication. To date, systemic therapy is a common approach to the chronic management of many diseases, including cancer. However, systemic toxicity is a major drawback, limiting the utility and effectiveness of such therapies. Recent research efforts in the development of drug delivery systems have concentrated on targeted delivery and controlled release of the drug or other agents in the target in order to increase the therapeutic ratio. IGDD is a therapeutic method where target localization and drug (or biologics) delivery are guided and monitored through noninvasive imaging. A full implementation of IGDD will require drugs (or biologics) that can be imaged or identified in the body as they enter the blood stream, are localized at the target, and are then released or otherwise activated to provide focal treatment. The goal in IGDD is to optimize local delivery of the therapeutic pharmaceutical to the target tissue and provide microanatomical and functional imaging feedback on the therapeutic process(es), including during treatment and monitoring.

The impetus for this FOA is to address the challenges associated with focal therapeutic delivery and the study of effectiveness and efficacy. Recent studies that focus on the engineering of targeted delivery systems and advanced imaging methodologies have shown the ability to quantify location and magnitude of targeted delivery. For instance, recent advances in applications of nanotechnologies to cancer have led to the development of nanocarriers that can deliver imaging contrast agents and therapeutics at the sub-cellular level. Furthermore, these nanoparticles may be functionalized to target certain tumors, and could be activated upon absorption of external energies or in response to chemical reactions. Nanoparticle constructs have the capability to be functionalized, to carry multiple imaging, targeting, and therapeutic moieties, to be multiplexed, to respond to various biological signals in real-time, thus making them particularly suitable for IGDD. Despite significant accomplishments in applications of nanotechnology in cancer, neuro-, and cardiovascular diseases, barriers remain in their successful implementation as clinical solutions. These translational barriers relate to variations in formulations and in vivo stability of nanoparticles, and limited data on the fate and toxicity of nanocarriers once they enter the body. Quantitative imaging may prove to be an invaluable tool to help overcome some of the barriers associated with the clinical translation of nanocarrier-enabled drug delivery as it will help provide quantitative data on nanoparticle behavior and distribution in vivo. Quantitative imaging methods may be used for target characterization (detection, localization, and pathology) to study the pharmacokinetics (PK) and pharmacodynamics (PD) of therapeutic uptake and efficacy, respectively, to determine the biodistribution and therapeutic effects across different spatial and functional resolution scales (molecular to organ level). Imaging and drug delivery systems supported through this FOA are not limited to nanotechnology based systems and they may include a variety of approaches including catheter based delivery, extracorporeal-triggered delivery and release of therapeutic vectors through the use of electromagnetic or ultrasonic radiation systems,  and biologically targeted small molecules labeled with imaging radioactive conjugates.