title: Tumor PO(2) changes during photodynamic therapy depend upon photosensitizer type and time after injection.
abstract: In this study, the vascular and tissue oxygen changes induced by photodynamic therapy in the RIF-1 tumor were examined, using electron paramagnetic resonance (EPR) oximetry. Two photosensitizers, including verteporfin (BPD-MA in a lipid-based formulation) and aminolevulinic acid-induced protoporphyrin IX (ALA-PPIX), were investigated with optical irradiation, sufficient to induce sub-curative damage in the tumor tissue, and the transient changes in PO(2) and vascular perfusion were examined. A large increase in tissue oxygenation (from 3 up to 9.5 mmHg) was observed when treated with ALA-PPIX based photodynamic therapy, which lasted during the treatment and a small residual increase that returned back to baseline levels by 48 h after treatment. With verteporfin-based photodynamic therapy, one group of animals was irradiated 15 min after injection and exhibited a small decrease in oxygenation relative to pre-irradiation levels. The second group was irradiated at 3 h after injection and exhibited a large increase in the average PO(2), (from 3 to 15 mmHg) by the end of the treatment. These observations indicate that photodynamic therapy significantly increases tissue PO(2) under certain treatment conditions, with the potential cause being either increased local blood flow or decreased local oxygen metabolic consumption due to cellular damage.
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA. pogue@dartmouth.edu
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pogue
authors.forename: Julia A
authors.initials: JA
authors.lastname: O'Hara
authors.forename: Isak A
authors.initials: IA
authors.lastname: Goodwin
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Wilmot
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Fournier
authors.forename: Altug R
authors.initials: AR
authors.lastname: Akay
authors.forename: Harold
authors.initials: H
authors.lastname: Swartz
mesh_terms: D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D008027:Light; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism*; D010100:Oxygen / Q000032:analysis* / Q000378:metabolism*; D010313:Partial Pressure; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000032:analysis / Q000145:classification* / Q000494:pharmacology*; D011166:Porphyrins / Q000032:analysis / Q000494:pharmacology; D011524:Protoporphyrins / Q000032:analysis / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000077362:Verteporfin
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D011524:Protoporphyrins; D000077362:Verteporfin; C028025:protoporphyrin IX; D010100:Oxygen