The prognosis of pancreatobiliary malignancies with biliary obstructions is generally dismal because of unresectability at the time of presentation and poor response to chemotherapy and radiotherapy. Intrabiliary stenting is currently the best option for the treatment of most malignant biliary obstructions. However, the short term durability of biliary stents necessitates repeated interventions and longer hospital stays with associated high economic burden. In addition, current techniques for systemic chemotherapy do not permit delivery of doses sufficient for effective response at the target sites without substantial undesired toxicities to other organ systems. In the present project, we aim to overcome these problems with currently available medical and surgical treatments of malignant common bile duct (CBD) obstructions. Based on our previous extensive experience with a novel intraluminal MR imaging (MRI)/radiofrequency heating (RFH) prototype system, we are going to establish a new interventional technique. This innovative approach involves (a) intrabiliary MRI-guided local delivery of high-dose chemotherapeutic agents into the CBD wall and adjacent tissues;and (b) intrabiliary MRI-guided, RFH-enhanced local chemotherapy of malignant CBD obstructions. To achieve this goal, we propose three milestones: (i) optimization of the new intrabiliary MRI/RFH prototype system;(ii) preclinical validation of the feasibility of using the new technology to guide and enhance chemotherapeutic drug delivery into the CBD wall and adjacent tissues;and (iii) translation of this novel technology to clinical practice to treat the patients with malignant biliary obstructions. We are convinced that the success of this project could lead to significant breakthroughs in the management of malignant biliary diseases using MRI/RFH-interactive interventional oncologic techniques. Further expansion of this new technology should pave the road to advances in other areas of clinical translational research, including heat-enhanced gene therapy, temperature-sensitive therapies using targeted nanoparticles and peptides, photodynamic therapy, and radiation therapy. Finally, the success of this project should lay the groundwork for development of new technologies to treat obstructive diseases in other luminal systems such as the urinary tract and gastrointestinal tract.

Public Health Relevance

The prognosis of pancreatobiliary malignancies with biliary obstructions is very poor because of unresectability at the time of presentation and poor response to chemotherapy and radiotherapy. We aim to overcome these problems by establishment of a new interventional technique, named Intrabiliary MRI-guided/radiofrequency heat- enhanced local chemotherapy. The success of this project could lead to significant breakthroughs in the management of malignant biliary disease using MR/RF-interactive interventional oncologic techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB012467-04
Application #
8605021
Study Section
Special Emphasis Panel (ZEB1)
Program Officer
Krosnick, Steven
Project Start
2011-02-15
Project End
2016-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Washington
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98195
Wu, Xia; Zhang, Feng; Hu, Peng et al. (2017) Radiofrequency heat-enhanced direct intratumoral chemotherapy for prostate cancer. Oncol Lett 14:7250-7256
Bai, Zhibin; Shi, Yaoping; Wang, Jianfeng et al. (2017) Multi-modality imaging-monitored creation of rat orthotopic pancreatic head cancer with obstructive jaundice. Oncotarget 8:54277-54284
Qiu, Longhua; Zhang, Feng; Shi, Yaoping et al. (2016) Gliomas: Motexafin Gadolinium-enhanced Molecular MR Imaging and Optical Imaging for Potential Intraoperative Delineation of Tumor Margins. Radiology 279:400-9
Sun, Jihong; Zhang, Shizheng; Jiang, Shaojie et al. (2016) Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography. J Biomed Nanotechnol 12:1709-23
Li, Yangyang; Zhou, Yurong; Li, Xiang et al. (2016) A Facile Approach to Upconversion Crystalline CaF2:Yb(3+),Tm(3+)@mSiO2 Nanospheres for Tumor Therapy. RSC Adv 6:38365-38370
Chen, Lumin; Sun, Jihong; Yang, Xiaoming (2016) Radiofrequency ablation-combined multimodel therapies for hepatocellular carcinoma: Current status. Cancer Lett 370:78-84
Wang, Jianfeng; Shi, Yaoping; Bai, Zhibin et al. (2016) Radiofrequency hyperthermia-enhanced herpes simplex virus-thymidine kinase/ganciclovir direct intratumoral gene therapy of hepatocellular carcinoma. Int J Hyperthermia :1-8
Luo, Jingfeng; Wu, Xiaotian; Zhou, Fei et al. (2016) Radiofrequency hyperthermia promotes the therapeutic effects on chemotherapeutic-resistant breast cancer when combined with heat shock protein promoter-controlled HSV-TK gene therapy: Toward imaging-guided interventional gene therapy. Oncotarget 7:65042-65051
Zhang, Feng; Bai, Zhibin; Shi, Yaoping et al. (2015) Interventional MRI-guided local delivery of agents into swine bile duct walls using MR-compatible needle-integrated balloon catheter system. NMR Biomed 28:679-84
Luo, Jingfeng; Luo, Yuxuan; Sun, Jihong et al. (2015) Adeno-associated virus-mediated cancer gene therapy: current status. Cancer Lett 356:347-56

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