ABSTRACT
BACKGROUND: 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. MATERIALS AND METHODS: Doxorubicin was aerosolized into the abdominal cavity of swine at a pressure of 12 mmHg CO2 at 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. RESULTS: 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). CONCLUSION: 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.
Subject(s)
Disease Models, Animal , Doxorubicin/administration & dosage , Doxorubicin/pharmacokinetics , Peritoneum/drug effects , Whole-Body Irradiation , Administration, Inhalation , Aerosols , Animals , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/pharmacokinetics , Male , Peritoneum/pathology , Peritoneum/radiation effects , Postmortem Changes , Pressure , Radiation Dosage , Swine , Tissue DistributionABSTRACT
AIM: To compare the impact of single fractional with bi-fractional irradiation on the depth of doxorubicin penetration into the normal tissue after pressurized intra-peritoneal aerosol chemotherapy (PIPAC) in our ex vivo model. MATERIALS AND METHODS: Fresh post mortem swine peritoneum was cut into 12 proportional sections. Two control samples were treated with PIPAC only (no irradiation), one sample on day 1, the other on day 2. Five samples were irradiated with 1, 2, 4, 7 or 14 Gy followed by PIPAC. Four samples were treated on day one with 0.5, 1, 2, 3.5 or 7 Gy and with the same radiation dose 24 h later followed by PIPAC. Doxorubicin was aerosolized in an ex vivo PIPAC model at 12 mmHg/36°C. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. RESULTS: Doxorubicin penetration (DP) after PIPAC for the control samples was 407 µm and 373 µm, respectively. DP for samples with single fraction irradiation was 396 µm after 1 Gy, 384 µm after 2 Gy, 327 µm after 4 Gy, 280 µm after 7 Gy and 243 µm after 14 Gy. DP for samples with 2 fractions of irradiation was 376 µm after 0.5+0.5 Gy, 363 µm after 1+1 Gy, 372 µm after 2+2 Gy, 341 µm after 3.5+3.5 and 301 µm after 7+7 Gy irradiation. Fractionating of the irradiation did not significantly change DP into normal tissue. CONCLUSION: Irradiation does not increase the penetration depth of doxorubicin into the normal tissue but might have a limiting impact on penetration and distribution of doxorubicin. Further studies are warranted to investigate the impact of addition of irradiation to PIPAC of tumor cells and to find out if irradiation can be used safely as chemopotenting agent for patients with peritoneal metastases treated with PIPAC.
