Richard Price, PhD, is a Professor of Biomedical Engineering, Radiation & Radiation Oncology and Research Director of the UVA Focused Ultrasound Center.
Q. When and how did you get interested in FUS?
I became interested in therapeutic ultrasound during my postdoc in the late 1990s. I collaborated with a clinical cardiology group in developing the use of contrast agent microbubbles for perfusion imaging. Using intravital microscopy, we were among the first groups to observe permeabilization of capillaries and subsequent nanoparticle delivery to ultrasound-targeted tissue.
Q. What are your areas of interest in FUS?
I am primarily interested in drug and gene delivery across the blood-brain barrier. However, we are also interested in using similar approaches to non-invasively enhance drug and gene delivery to skeletal muscle to promote new blood vessel growth. We have also performed projects centered on using the mechanical effects of ultrasound-activated microbubbles to ablate tumors.
Q. What mechanisms and clinical indications do you study?
Clinical indications in the brain are primary brain tumors, metastatic brain tumors, and neurodegenerative disease. We are also using melanoma models to develop focused ultrasound for immunotherapy. Our work in targeted delivery skeletal muscle is most closely linked to revascularization approaches for peripheral arterial disease.
Q. How large is your research staff/team?
About 10 people total, primarily graduate students. We also have a strong group of undergraduate researchers and a full-time research scientist.
Q. Who are your internal and external collaborators?
They are listed in the story above (Hanes, Abounader, Purow, Bullock, and Engelhard).
Q. What do you see as impediments to your success?
As with any project, we want to achieve the results that we are seeking: high delivery levels with acceptable safety.
Q. What is your research wish list?
We are the first group to deliver a gene across the BBB with focused ultrasound using a non-viral brain-penetrating nanoparticle. We are currently using GDNF but are also exploring other therapeutic options. GDNF has been studied in this context for a long-time. I agree with Justin – using this technology to help people with Parkinson’s would be amazing.
Q. Did the Foundation play a role in this project?
Yes, the Foundation supported our early validating work.
Q. Looking ahead, what comes next?
More basic research and clinical trials. As Justin commented, the progression will be safety studies, dosage studies, GLP/GNP condition studies, and then toxicology studies. All of this must be done before asking the Food and Drug Administration (FDA) to initiate human clinical trials.
Q. What are your focused ultrasound research funding sources?
- National Institutes of Health – R01 (PI – Price) Immunotherapeutic Nanoparticle Delivery to Melanoma with Focused Ultrasound. June 2015 – May 2020. Total costs of $2,600,000.
- National Institutes of Health R01 (PI – Price) MR-Guided Delivery of miRNA-Bearing Nanoparticles to Glioblastoma with Focused Ultrasound. May 2015 – February 2019. Total costs of $2,500,000.
- MRA/CRI/FUSF (PI – Bullock) Immunotherapeutic Antibody Delivery to Brain Tumors with Focused Ultrasound. May 2015 – April 2018. Total costs of $375,000.
- Focused Ultrasound Foundation (PI – Price) Minimally-Invasive Therapy for Parkinson’s Disease Achieved by Focused Ultrasound–Targeted Delivery of Non-Viral Gene Nanocarriers. March 2015 – February 2016. Total costs of $100,000.
- National Institutes of Health – R03 (PI – Price) Bevacizumab Delivery to Glioblastoma with MR-Guided Focused Ultrasound. April 2013 – March 2016. Total costs of $153,000.
- National Institutes of Health – R01 (PI – Abounader) Novel RTK Targeting Strategies in Glioblastoma. September 2013 – August 2018. Total costs of ~$2,000,000.
- National Institutes of Health – R01 (PI – Price) Brain Tumor-Penetrating Nanoparticle Delivery with MR-Guided Focused Ultrasound. May 2012 – March 2017. Total costs of $3,200,000.
Q. What are your key FUS publications?
- Noninvasive Delivery of Stealth Brain Penetrating Nanoparticles Across the Blood-Brain Barrier with MR Image-Guided Focused Ultrasound. J Cont Rel. 189:123-132.
- Ultrasound-Activated Agents Comprised of 5FU-Bearing Nanoparticles Bonded to Microbubbles Inhibit Solid Tumor Growth and Improve Survival. Molecular Therapy. 22:321-8.
- Markedly Enhanced Skeletal Muscle Transfection Achieved by the Ultrasound-Targeted Delivery of Non-Viral Gene Nanocarriers with Microbubbles. J Cont Rel. 162:414-421.
- Covalently Linking Poly (Lactic-co-Glycolic Acid) Nanoparticles to Microbubbles Before Intravenous Injection Improves Their Ultrasound-Targeted Delivery to Skeletal Muscle. Small. 7: 1227-1235.
- Inhibition of Glioma Growth by Microbubble Activation in a Subcutaneous Model Using Low Duty Cycle Ultrasound Without Significant Heating. J Neurosurg 2011;114:1654-1661.
- Price RJ, Skyba DM, Kaul S, Skalak TC. Delivery of Colloidal Particles and Red Blood Cells to Tissue Through Microvessel Ruptures Created by Targeted Microbubble Destruction with Ultrasound. Circulation 1998;98:1264-1267.
- Song J, Chappell JC, Qi M, Van Gieson EJ, Kaul S, Price RJ. Influence of Injection Site, Microvascular Pressure, and Ultrasound Variables on Microbubble Mediated Delivery of Microspheres to Muscle. J Am Coll Cardiol 2002;39:726-731.
- Chappell JC, Song J, Burke CW, Klibanov AL, Price RJ. Targeted Delivery of Nanoparticles Bearing FGF-2 by Ultrasonic Microbubble Destruction for Therapeutic Arteriogenesis. Small 2008;4:1769-1777.
- Moyer LC, Timbie KF, Sheeran PS, Price RJ, Miller GW, Dayton PA. High Intensity Focused Ultrasound Ablation Enhancement In Vivo via Phase-shift Nanodroplets Compared to Microbubbles. J Therapeutic Ultrasound 2015 doi: 10.1186/s40349-015-0029-4.