title: Carbogen breathing differentially enhances blood plasma volume and 5-fluorouracil uptake in two murine colon tumor models with a distinct vascular structure.
abstract: For the systemic treatment of colorectal cancer, 5-fluorouracil (FU)-based chemotherapy is the standard. However, only a subset of patients responds to chemotherapy. Breathing of carbogen (95% O2 and 5% CO2) may increase the uptake of FU through changes in tumor physiology. This study aims to monitor in animal models in vivo the effects of carbogen breathing on tumor blood plasma volume, pH, and energy status, and on FU uptake and metabolism in two colon tumor models C38 and C26a, which differ in their vascular structure and hypoxic status. Phosphorus-31 magnetic resonance spectroscopy (MRS) was used to assess tumor pH and energy status, and fluorine-19 MRS was used to follow FU uptake and metabolism. Advanced magnetic resonance imaging methods using ultrasmall particles of iron oxide were performed to assess blood plasma volume. The results showed that carbogen breathing significantly decreased extracellular pH and increased tumor blood plasma volume and FU uptake in tumors. These effects were most significant in the C38 tumor line, which has the largest relative vascular area. In the C26a tumor line, carbogen breathing increased tumor growth delay by FU. In this study, carbogen breathing also enhanced systemic toxicity by FU.
authors.affiliation: Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. h.vanlaarhoven@onco.umcn.nl
authors.forename: Hanneke W M
authors.initials: HW
authors.lastname: van Laarhoven
authors.forename: Giulio
authors.initials: G
authors.lastname: Gambarota
authors.forename: Jasper
authors.initials: J
authors.lastname: Lok
authors.forename: Martin
authors.initials: M
authors.lastname: Lammens
authors.forename: Yvonne L M
authors.initials: YL
authors.lastname: Kamm
authors.forename: Theo
authors.initials: T
authors.lastname: Wagener
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: Albert J
authors.initials: AJ
authors.lastname: van der Kogel
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000737:chemistry*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes / Q000627:therapeutic use; D005472:Fluorouracil / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000737:chemistry*; D010761:Phosphorus Radioisotopes; D010949:Plasma / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012119:Respiration
chemical_list: D000964:Antimetabolites, Antineoplastic; D005462:Fluorine Radioisotopes; D010761:Phosphorus Radioisotopes; D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; C011700:carbogen; D010100:Oxygen; D005472:Fluorouracil