title: Oxygen depletion during and after mTHPC-mediated photodynamic therapy in RIF1 and H-MESO1 tumors.
abstract: During photodynamic therapy (PDT), low oxygenation levels, induced both by oxygen consumption and by vascular occlusion, can lead to an inefficient photochemical reaction that may compromise the efficacy of PDT. In the present studies, tumor oxygenation was measured before, during and after meta-tetrahydroxyphenylchlorin (mTHPC)-mediated PDT of murine RIF1 tumors and human mesothelioma xenografts (H-MESO1). Tumor pO2 was measured in real time with Eppendorf polarography, and the extent of relative hypoxia at specific times was measured by immunohistochemical staining. Significant decreases in median pO2 values, as well as an increase in the number of values below 2.5 mmHg, were seen during and after PDT in RIF1 tumors, although there was a large intertumoral variation. Tumor pO2 values did not change significantly in H-MESO1 tumors. Staining with antibodies against the hypoxia marker EF3 showed significant increases in relative hypoxia after PDT in both tumor types compared with separate groups of untreated controls. Our results are consistent with PDT-induced oxygen depletion (reduced pO2) leading to an increase in relative hypoxia in RIF1 tumors. Extensive necrosis in the H-MESO1 tumors may have prevented the detection of PDT-induced hypoxia using the Eppendorf polarographic needle, whereas immunohistochemistry did reveal increases in relative hypoxia.
authors.affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Schouwink
authors.forename: Hugo
authors.initials: H
authors.lastname: Oppelaar
authors.forename: Marjan
authors.initials: M
authors.lastname: Ruevekamp
authors.forename: Martin
authors.initials: M
authors.lastname: van der Valk
authors.forename: Guus
authors.initials: G
authors.lastname: Hart
authors.forename: Paul
authors.initials: P
authors.lastname: Rijken
authors.forename: Paul
authors.initials: P
authors.lastname: Baas
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Stewart
mesh_terms: D000818:Animals; D005260:Female; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D010313:Partial Pressure; D010778:Photochemotherapy / Q000009:adverse effects*; D014407:Tumor Cells, Cultured
chemical_list: D010100:Oxygen