Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator

Ning Cao, Seung Hyun Song, Teimour Maleki, Michael Shaffer, Keith M. Stantz, Minsong Cao, Chinghai Kao, Marc Mendonca, Babak Ziaie, Song Chu Ko

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)431-437
Number of pages7
JournalRadiation Research
Volume185
Issue number4
DOIs
StatePublished - Apr 1 2016

Fingerprint

Pancreatic Neoplasms
Heterografts
generators
tumors
cancer
Oxygen
oxygen
Neoplasms
hypoxia
mice
radiation therapy
Radiotherapy
Nude Rats
oxygen production
Radiation Dosage
Equipment and Supplies
oxygenation
radiation
ultrasonic radiation
chemotherapy

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Cao, N., Song, S. H., Maleki, T., Shaffer, M., Stantz, K. M., Cao, M., ... Ko, S. C. (2016). Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator. Radiation Research, 185(4), 431-437. https://doi.org/10.1667/RR14149.1

Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator. / Cao, Ning; Song, Seung Hyun; Maleki, Teimour; Shaffer, Michael; Stantz, Keith M.; Cao, Minsong; Kao, Chinghai; Mendonca, Marc; Ziaie, Babak; Ko, Song Chu.

In: Radiation Research, Vol. 185, No. 4, 01.04.2016, p. 431-437.

Research output: Contribution to journalArticle

Cao, N, Song, SH, Maleki, T, Shaffer, M, Stantz, KM, Cao, M, Kao, C, Mendonca, M, Ziaie, B & Ko, SC 2016, 'Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator', Radiation Research, vol. 185, no. 4, pp. 431-437. https://doi.org/10.1667/RR14149.1
Cao N, Song SH, Maleki T, Shaffer M, Stantz KM, Cao M et al. Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator. Radiation Research. 2016 Apr 1;185(4):431-437. https://doi.org/10.1667/RR14149.1
Cao, Ning ; Song, Seung Hyun ; Maleki, Teimour ; Shaffer, Michael ; Stantz, Keith M. ; Cao, Minsong ; Kao, Chinghai ; Mendonca, Marc ; Ziaie, Babak ; Ko, Song Chu. / Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator. In: Radiation Research. 2016 ; Vol. 185, No. 4. pp. 431-437.
@article{9f2415378dae4f41a4d1f5630c503ee5,
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.",
author = "Ning Cao and Song, {Seung Hyun} and Teimour Maleki and Michael Shaffer and Stantz, {Keith M.} and Minsong Cao and Chinghai Kao and Marc Mendonca and Babak Ziaie and Ko, {Song Chu}",
year = "2016",
month = "4",
day = "1",
doi = "10.1667/RR14149.1",
language = "English (US)",
volume = "185",
pages = "431--437",
journal = "Radiation Research",
issn = "0033-7587",
publisher = "Radiation Research Society",
number = "4",

}

TY - JOUR

T1 - Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator

AU - Cao, Ning

AU - Song, Seung Hyun

AU - Maleki, Teimour

AU - Shaffer, Michael

AU - Stantz, Keith M.

AU - Cao, Minsong

AU - Kao, Chinghai

AU - Mendonca, Marc

AU - Ziaie, Babak

AU - Ko, Song Chu

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84966687268&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84966687268&partnerID=8YFLogxK

U2 - 10.1667/RR14149.1

DO - 10.1667/RR14149.1

M3 - Article

VL - 185

SP - 431

EP - 437

JO - Radiation Research

JF - Radiation Research

SN - 0033-7587

IS - 4

ER -