title: Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator.
abstract: Over the past decades, little progress has been made to improve the extremely low survival rates in pancreatic cancer patients. Extreme hypoxia observed in pancreatic tumors contributes to the aggressive and metastatic characteristics of this tumor and can reduce the effectiveness of conventional radiation therapy and chemotherapy. In an attempt to reduce hypoxia-induced obstacles to effective radiation treatment, we used a novel device, the implantable micro-oxygen generator (IMOG), for in situ tumor oxygenation. After subcutaneous implantation of human pancreatic xenograft tumors in athymic rats, the IMOG was wirelessly powered by ultrasonic waves, producing 30 μA of direct current (at 2.5 V), which was then utilized to electrolyze water and produce oxygen within the tumor. Significant oxygen production by the IMOG was observed and corroborated using the NeoFox oxygen sensor dynamically. To test the radiosensitization effect of the newly generated oxygen, the human pancreatic xenograft tumors were subcutaneously implanted in nude mice with either a functional or inactivated IMOG device. The tumors in the mice were then exposed to ultrasonic power for 10 min, followed by a single fraction of 5 Gy radiation, and tumor growth was monitored thereafter. The 5 Gy irradiated tumors containing the functional IMOG exhibited tumor growth inhibition equivalent to that of 7 Gy irradiated tumors that did not contain an IMOG. Our study confirmed that an activated IMOG is able to produce sufficient oxygen to radiosensitize pancreatic tumors, enhancing response to single-dose radiation therapy.
authors.affiliation: Schools of a   Health Sciences.|d   Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington; Departments of.
authors.forename: Ning
authors.initials: N
authors.lastname: Cao
authors.affiliation: b   Electrical and Computer Engineering and.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Song
authors.affiliation: c   Birck Nanotechnology Center, Purdue University, W. Lafayette, Indiana;
authors.forename: Teimour
authors.initials: T
authors.lastname: Maleki
authors.affiliation: Schools of a   Health Sciences.
authors.forename: Michael
authors.initials: M
authors.lastname: Shaffer
authors.affiliation: Schools of a   Health Sciences.|e   Radiology.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Stantz
authors.affiliation: f   Radiation Oncology and.|h   Radiation Oncology, UCLA Medical Center, Los Angeles, California; and.
authors.forename: Minsong
authors.initials: M
authors.lastname: Cao
authors.affiliation: g   Urology, Indiana University School of Medicine, Indianapolis, Indiana;
authors.forename: Chinghai
authors.initials: C
authors.lastname: Kao
authors.affiliation: f   Radiation Oncology and.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Mendonca
authors.affiliation: b   Electrical and Computer Engineering and.
authors.forename: Babak
authors.initials: B
authors.lastname: Ziaie
authors.affiliation: f   Radiation Oncology and.|i   Radiation Oncology, IU Health Arnett Hospital, Lafayette, Indiana.
authors.forename: Song-Chu
authors.initials: SC
authors.lastname: Ko
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000528:radiation effects; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D006801:Humans; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D019736:Prostheses and Implants; D011836:Radiation Tolerance; D051381:Rats; D013997:Time Factors
chemical_list: D010100:Oxygen