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Title: Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models

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 gantrymore » 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.« less

Authors:
 [1];  [2]; ; ;  [3]; ; ;  [4];  [5];  [6]; ; ;  [3];  [3]
  1. Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins School of Medicine, Baltimore, MD (United States)
  2. Tri-Institutional Training Program in Laboratory Animal Medicine and Science, Memorial Sloan-Kettering Cancer Center (MSKCC), Weill Cornell Medical College, The Rockefeller University, New York, NY (United States)
  3. Department of Medical Physics, MSKCC, New York, NY (United States)
  4. Department of Medicine, MSKCC, New York, NY (United States)
  5. Molecular Pharmacology and Chemistry Program, MSKCC, New York, NY (United States)
  6. (Urology), Skåne University Hospital, Malmö (Sweden)
Publication Date:
OSTI Identifier:
22458793
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 93; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANIMAL TISSUES; BIOMEDICAL RADIOGRAPHY; COMPARATIVE EVALUATIONS; COMPUTERIZED TOMOGRAPHY; GROWTH; MICE; MONITORING; NEOPLASMS; NMR IMAGING; PANCREAS; PLANNING; RADIATION DOSES; RADIOTHERAPY; X RADIATION

Citation Formats

Thorek, Daniel L.J., E-mail: dthorek1@jhmi.edu, Kramer, Robin M., Chen, Qing, Jeong, Jeho, Lupu, Mihaela E., Lee, Alycia M., Moynahan, Mary E., Lowery, Maeve, Ulmert, David, Department of Surgery, Zanzonico, Pat, Deasy, Joseph O., Humm, John L., and Russell, James, E-mail: russellj@mskcc.org. Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models. United States: N. p., 2015. Web. doi:10.1016/J.IJROBP.2015.06.001.
Thorek, Daniel L.J., E-mail: dthorek1@jhmi.edu, Kramer, Robin M., Chen, Qing, Jeong, Jeho, Lupu, Mihaela E., Lee, Alycia M., Moynahan, Mary E., Lowery, Maeve, Ulmert, David, Department of Surgery, Zanzonico, Pat, Deasy, Joseph O., Humm, John L., & Russell, James, E-mail: russellj@mskcc.org. Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models. United States. doi:10.1016/J.IJROBP.2015.06.001.
Thorek, Daniel L.J., E-mail: dthorek1@jhmi.edu, Kramer, Robin M., Chen, Qing, Jeong, Jeho, Lupu, Mihaela E., Lee, Alycia M., Moynahan, Mary E., Lowery, Maeve, Ulmert, David, Department of Surgery, Zanzonico, Pat, Deasy, Joseph O., Humm, John L., and Russell, James, E-mail: russellj@mskcc.org. Thu . "Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models". United States. doi:10.1016/J.IJROBP.2015.06.001.
@article{osti_22458793,
title = {Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models},
author = {Thorek, Daniel L.J., E-mail: dthorek1@jhmi.edu and Kramer, Robin M. and Chen, Qing and Jeong, Jeho and Lupu, Mihaela E. and Lee, Alycia M. and Moynahan, Mary E. and Lowery, Maeve and Ulmert, David and Department of Surgery and Zanzonico, Pat and Deasy, Joseph O. and Humm, John L. and Russell, James, E-mail: russellj@mskcc.org},
abstractNote = {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.},
doi = {10.1016/J.IJROBP.2015.06.001},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 2,
volume = 93,
place = {United States},
year = {2015},
month = {10}
}