title: Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins School of Medicine, Baltimore, MD. Electronic address: dthorek1@jhmi.edu.
authors.forename: Daniel L J
authors.initials: DL
authors.lastname: Thorek
authors.affiliation: 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.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Kramer
authors.affiliation: Department of Medical Physics, MSKCC, New York, NY.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Medical Physics, MSKCC, New York, NY.
authors.forename: Jeho
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Department of Medical Physics, MSKCC, New York, NY.
authors.forename: Mihaela E
authors.initials: ME
authors.lastname: Lupu
authors.affiliation: Department of Medicine, MSKCC, New York, NY.
authors.forename: Alycia M
authors.initials: AM
authors.lastname: Lee
authors.affiliation: Department of Medicine, MSKCC, New York, NY.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Moynahan
authors.affiliation: Department of Medicine, MSKCC, New York, NY.
authors.forename: Maeve
authors.initials: M
authors.lastname: Lowery
authors.affiliation: Molecular Pharmacology and Chemistry Program, MSKCC, New York, NY; Department of Surgery (Urology), Skåne University Hospital, Malmö, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Ulmert
authors.affiliation: Department of Medical Physics, MSKCC, New York, NY.
authors.forename: Pat
authors.initials: P
authors.lastname: Zanzonico
authors.affiliation: Department of Medical Physics, MSKCC, New York, NY.
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Deasy
authors.affiliation: Department of Medical Physics, MSKCC, New York, NY.
authors.forename: John L
authors.initials: JL
authors.lastname: Humm
authors.affiliation: Department of Medical Physics, MSKCC, New York, NY. Electronic address: russellj@mskcc.org.
authors.forename: James
authors.initials: J
authors.lastname: Russell
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D064593:Heterografts; D006657:Histones / Q000032:analysis; D007274:Injections, Intraperitoneal; D008279:Magnetic Resonance Imaging / Q000379:methods; D008488:Medical Illustration; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D061089:Radiotherapy, Image-Guided / Q000379:methods; D011897:Random Allocation; D014057:Tomography, X-Ray Computed / Q000379:methods*; D014183:Transplantation, Heterologous / Q000379:methods; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D006657:Histones; C475961:gamma-H2AX protein, mouse