title: Effect of Whole-abdominal Irradiation on Penetration Depth of Doxorubicin in Normal Tissue After Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in a Post-mortem Swine Model.
abstract: This study was performed to evaluate the impact of whole-abdominal irradiation on local penetration of doxorubicin into the peritoneum and the abdominal organs in a post-mortem swine model.
  
  
  
  Doxorubicin was aerosolized into the abdominal cavity of swine at a pressure of 12 mmHg CO2at room temperature (25°). One swine was subjected to pressurized intraperitoneal aerosol chemotherapy (PIPAC) using Micropump©without irradiation; the second one received 2 Gy and the third one 7 Gy whole-abdominal irradiation, 15 min prior to PIPAC application. Samples of the peritoneal surface were extracted at different positions from within the abdominal cavity. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections.
  
  
  
  The depth of penetration of doxorubicin was found to be wide-ranging, between 17 μm on the surface of the stomach and 348 μm in the small intestine. The penetration depth into the small intestine was 348 μm, 312 μm and 265 μm for PIPAC alone, PIPAC with 2 Gy irradiation and PIPAC with 7 Gy irradiation, respectively (p<0.05). The penetration into the liver was 64 μm, 55 μm and 40 μm, respectively (p=0.05).
  
  
  
  Irradiation was not found to increase the depth of doxorubicin penetration into normal tissue in the post-mortem swine model. A reduction of doxorubicin penetration was observed after application of higher irradiation doses. Further studies are warranted to determine if irradiation can be used safely as chemopotentiating agent for patients with peritoneal metastases treated with PIPAC.
authors.affiliation: Department of Neuroanatomy, Ruhr University, Bochum, Germany.
authors.forename: Veria
authors.initials: V
authors.lastname: Khosrawipour
authors.affiliation: Department of General Surgery, Marien Hospital Herne, Ruhr University, Bochum, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Khosrawipour
authors.affiliation: Department of Radiation Oncology, Marien Hospital Herne, Ruhr University, Bochum, Germany.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Hedayat-Pour
authors.affiliation: Department of Hematology & Medical Oncology, Marien Hospital Herne, Ruhr University, Bochum, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Diaz-Carballo
authors.affiliation: Department of Nuclear Medicine, University Clinic Essen, Essen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bellendorf
authors.affiliation: Department of Radiation Oncology, Marien Hospital Herne, Ruhr University, Bochum, Germany.
authors.forename: Hugo
authors.initials: H
authors.lastname: Böse-Ribeiro
authors.affiliation: Department of Radiation Oncology, Marien Hospital Herne, Ruhr University, Bochum, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Mücke
authors.affiliation: Department of Neuroanatomy, Ruhr University, Bochum, Germany.
authors.forename: Nirushika
authors.initials: N
authors.lastname: Mohanaraja
authors.affiliation: Department of Radiation Oncology, Marien Hospital Herne, Ruhr University, Bochum, Germany.
authors.forename: Irenäus Anton
authors.initials: IA
authors.lastname: Adamietz
authors.affiliation: Department of Radiation Oncology, Marien Hospital Herne, Ruhr University, Bochum, Germany khfmed@yahoo.com.
authors.forename: Khashayar
authors.initials: K
authors.lastname: Fakhrian
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D010537:Peritoneum / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D011180:Postmortem Changes; D011312:Pressure; D011829:Radiation Dosage; D013552:Swine; D014018:Tissue Distribution; D014916:Whole-Body Irradiation
chemical_list: D000336:Aerosols; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
keywords: PIPAC; Post-mortem swine model; intraperitoneal chemotherapy; peritoneal carcinomatosis; whole-abdominal radiation