In this proposal, we seek to develop a set of new tools to assess and enhance the efficacy of anti-cancer therapies that have immediate clinical relevance. In particular, we have developed and embedded methods for real-time quantitative parametric ultrasound imaging of vascular volume/density and flow rate to assess tumor therapies in a clinical scanner and will evaluate and validate those methods here.
Our aims for the assessment of therapeutic efficacy include: evaluate the use of ultrasound methods to estimate flow rate and vascular volume/density in the assessment of therapeutic response;migrate the methods to real-time, on-scanner measurement;and use ultrasound feedback together with histology to optimize treatment with a cocktail of appropriate drugs. Further, we endeavor to enhance therapeutic efficacy by increasing vascular permeability and nanoparticle accumulation using ultrasound. In our initial studies using 2-minute insonation with a low thermal dose, we found that accumulation of liposomes in an insonified tumor increases ~three-fold to as much as 22%ID/g and the accumulation within insonified muscle or lymph nodes increased 3-10 fold. At our site and others the combination of ablative therapies and nanoparticle drug administration has already begun and as MR-guided ultrasound enters the clinic, this combination will be used more frequently.
Our aims for the enhancement of efficacy with ultrasound are to: determine the mechanism for ultrasound-enhanced increases in vascular permeability;maximize ultrasound enhancement of the accumulation of particles in a tumor and surrounding tissue;establish a pharmacokinetic model that describes ultrasound-enhanced permeability;and compare the efficacy of particle injection immediately before and after ultrasound and incorporate US- enhanced delivery into a strategy that includes an anti-angiogenic drug, chemotherapeutics an ultrasound monitoring of response.

Public Health Relevance

Currently, one in 4 deaths in the United States is due to cancer. Many new therapeutic strategies can be employed;however, efficient methods to test these strategies are required. We are completing the development of an ultrasound-based strategy for the assessment of therapeutic efficacy that provides quantitative, repeatable and user-independent measures. Further, we are developing methods to enhance therapeutic efficacy using ultrasound by enhancing the accumulation of drug within the tumor.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
4R01CA134659-03
Application #
8192907
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Farahani, Keyvan
Project Start
2009-05-17
Project End
2013-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
3
Fiscal Year
2011
Total Cost
$490,434
Indirect Cost
Name
University of California Davis
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
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