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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Farahani, Keyvan
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University of California Davis
Biomedical Engineering
Schools of Engineering
United States
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Kakwere, Hamilton; Ingham, Elizabeth S; Allen, Riley et al. (2017) Toward Personalized Peptide-Based Cancer Nanovaccines: A Facile and Versatile Synthetic Approach. Bioconjug Chem 28:2756-2771
Foiret, Josquin; Zhang, Hua; Ilovitsh, Tali et al. (2017) Ultrasound localization microscopy to image and assess microvasculature in a rat kidney. Sci Rep 7:13662
Fite, Brett Z; Kheirolomoom, Azadeh; Foiret, Josquin L et al. (2017) Dynamic contrast enhanced MRI detects changes in vascular transport rate constants following treatment with thermally-sensitive liposomal doxorubicin. J Control Release 256:203-213
Pollard, Rachel E; Watson, Katherine D; Hu, Xiaowen et al. (2017) Feasibility of quantitative contrast ultrasound imaging of bladder tumors in dogs. Can Vet J 58:70-72
Zhang, Hua; Ingham, Elizabeth S; Gagnon, M Karen J et al. (2017) In vitro characterization and in vivo ultrasound molecular imaging of nucleolin-targeted microbubbles. Biomaterials 118:63-73
Liu, Yu; Liu, Jingfei; Fite, Brett Z et al. (2017) Supersonic transient magnetic resonance elastography for quantitative assessment of tissue elasticity. Phys Med Biol 62:4083-4106
Baikejiang, Reheman; Zhao, Yue; Fite, Brett Z et al. (2017) Anatomical image-guided fluorescence molecular tomography reconstruction using kernel method. J Biomed Opt 22:55001
Silvestrini, Matthew T; Ingham, Elizabeth S; Mahakian, Lisa M et al. (2017) Priming is key to effective incorporation of image-guided thermal ablation into immunotherapy protocols. JCI Insight 2:e90521
Lin, Tzu-Yin; Li, Yuanpei; Liu, Qiangqiang et al. (2016) Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer. Biomaterials 104:339-51
Liu, Jingfei; Foiret, Josquin; Stephens, Douglas N et al. (2016) Development of a spherically focused phased array transducer for ultrasonic image-guided hyperthermia. Phys Med Biol 61:5275-96

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