Reverse-contrast imaging and targeted radiation therapy of advanced pancreatic cancer models

Daniel L J Thorek, Robin M. Kramer, Qing Chen, Jeho Jeong, Mihaela E. Lupu, Alycia M. Lee, Mary E. Moynahan, Maeve Lowery, David Ulmert, Pat Zanzonico, Joseph O. Deasy, John L. Humm, James Russell

Research output: Contribution to journalArticle

Abstract

Purpose To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by x-ray CT. With this technique we delineated the pancreas and both orthotopic xenografts and genetically engineered disease. Computed tomographic imaging was validated by comparison with magnetic resonance imaging. Therapeutic radiation was delivered via a 1-cm diameter field. Selective x-ray radiation therapy of the noninvasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360° arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic x-ray radiation therapy to orthotopic tumors. Results Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times after treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions This advance permits evaluation of radiation planning and dosing parameters. Accurate noninvasive longitudinal imaging and monitoring of tumor progression and therapeutic response in preclinical models is now possible and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response.

Original languageEnglish (US)
Pages (from-to)444-453
Number of pages10
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume93
Issue number2
DOIs
StatePublished - Oct 1 2015

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Pancreatic Neoplasms
radiation therapy
Radiotherapy
tumors
cancer
pancreas
Pancreas
gantry cranes
tomography
Neoplasms
Tomography
X-Rays
Therapeutics
mice
planning
delivery
radiation
Radiation
x rays
delineation

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

Reverse-contrast imaging and targeted radiation therapy of advanced pancreatic cancer models. / Thorek, Daniel L J; Kramer, Robin M.; Chen, Qing; Jeong, Jeho; Lupu, Mihaela E.; Lee, Alycia M.; Moynahan, Mary E.; Lowery, Maeve; Ulmert, David; Zanzonico, Pat; Deasy, Joseph O.; Humm, John L.; Russell, James.

In: International Journal of Radiation Oncology, Biology, Physics, Vol. 93, No. 2, 01.10.2015, p. 444-453.

Research output: Contribution to journalArticle

Thorek, DLJ, Kramer, RM, Chen, Q, Jeong, J, Lupu, ME, Lee, AM, Moynahan, ME, Lowery, M, Ulmert, D, Zanzonico, P, Deasy, JO, Humm, JL & Russell, J 2015, 'Reverse-contrast imaging and targeted radiation therapy of advanced pancreatic cancer models', International Journal of Radiation Oncology, Biology, Physics, vol. 93, no. 2, pp. 444-453. https://doi.org/10.1016/j.ijrobp.2015.06.001
Thorek, Daniel L J ; Kramer, Robin M. ; Chen, Qing ; Jeong, Jeho ; Lupu, Mihaela E. ; Lee, Alycia M. ; Moynahan, Mary E. ; Lowery, Maeve ; Ulmert, David ; Zanzonico, Pat ; Deasy, Joseph O. ; Humm, John L. ; Russell, James. / Reverse-contrast imaging and targeted radiation therapy of advanced pancreatic cancer models. In: International Journal of Radiation Oncology, Biology, Physics. 2015 ; Vol. 93, No. 2. pp. 444-453.
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