Professor of Radiology and BME; Director, CWRU Center for Imaging Research Case Western Reserve University Cleveland, Ohio
The microenvironment of most solid tumors is hallmarked by increased vascular permeability. This characteristic has been the premise of numerous nanomedicine-based drug delivery systems, which have sought to exploit the long-standing concept of the enhanced permeability and retention (EPR) effect as a primary method for delivering active pharmaceutical ingredients to tumors. However, this approach has not yielded the expected results in clinical applications of these agents. Noninvasive imaging techniques present a potential solution to this issue. With the help of imaging-based biomarkers of vascular permeability and relevant companion diagnostic contrast agents, imaging can help improve the effectiveness of treatments by predicting which patients are likely to respond positively to nanomedicine therapies. Several modalities including MRI and CT as well as optical imaging have been investigated for this purpose, with some promising outcomes. However, barriers such high cost and ionizing radiation have somewhat dampened enthusiasm for these approaches. To overcome these challenges, our group has begun to investigate ultrasound (US) imaging as an alternative modality in this area. Recent research has shown that gas-core nanoparticles, or nanobubbles, can serve as a robust contrast agent for ultrasound, and these scans can provide insights into tumor transport of nanomedicines at near real time scale and at high spatial resolution. Accordingly, we have applied this strategy to identify those tumor microenvironments that are prone to nanoparticle extravasation and retention. Our early results suggest that nanobubble-based contrast enhanced ultrasound can be used to derive parameters that collectively predict accumulation of drug-loaded liposomes (Doxil) in tumors, and subsequently these parameters can be used to successfully predict tumor response to therapy. The use of ultrasound to forecast the effectiveness of nanoparticles in cancer treatment could enhance the selection of patients who are likely to respond positively. This, in turn, could become a key factor in advancing personalized medicine.
Learning Objectives:
Upon completion of, participants will be able to understand various imaging modalities used to image nanomedicine trasnport in tumors and how these tools can add value to drug discovery and development.
Upon completion of, participants will be able appreciate where the use of imaging and companion diagnostics brings translational impact.
Upon completion of, participants will be able to critically assess technological and practical considerations limitations and explore future applications of this novel technology in drug R&D.
