title: Evaluation of the 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) mediated photodynamic therapy by macroscopic singlet oxygen modeling.
abstract: Photodynamic therapy (PDT) is known as a non-invasive treatment modality that is based on photochemical reactions between oxygen, photosensitizer, and a special wavelength of light. However, a dosimetric predictor for PDT outcome is still elusive because current dosimetric quantities do not account for the differences in the PDT oxygen consumption rate for different fluence rates. In this study, we evaluate several dose metrics, total fluence, photobleaching ratio, PDT dose, and mean reacted singlet oxygen (mean [1O2]rx) for predicting the PDT outcome and a clinically relevant tumor re-growth endpoint. For this reason, radiation-induced fibrosarcoma (RIF) mice tumors are treated with 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) and different in-air fluences (30 J/cm2, 50 J/cm2, 135 J/cm2, 250 J/cm2, and 350 J/cm2) and in-air fluence rates (20, 50, 75, 150 mW/cm2). Explicit measurements of HPPH and oxygen concentration as well as tissue optical properties are performed pre- and post-treatment. Then, this information is incorporated into a macroscopic model to calculate the photobleaching, PDT dose, and mean [1O2]rx. Changes in tumor volume are tracked following the treatment and compared with the dose metrics. The correlation demonstrates that mean [1O2]rxserves as a better dosimetric quantity for predicting treatment outcome and a clinically relevant tumor re-growth endpoint.
authors.affiliation: University of Pennsylvania, School of Medicine, Department of Radiation Oncology, 3400 Civic Center Boulevard TRC 4W, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Rozhin
authors.initials: R
authors.lastname: Penjweini
authors.affiliation: University of Pennsylvania, School of Medicine, Department of Radiation Oncology, 3400 Civic Center Boulevard TRC 4W, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Kim
authors.affiliation: University of Pennsylvania, School of Medicine, Department of Radiation Oncology, 3400 Civic Center Boulevard TRC 4W, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Baochang
authors.initials: B
authors.lastname: Liu
authors.affiliation: University of Pennsylvania, School of Medicine, Department of Radiation Oncology, 3400 Civic Center Boulevard TRC 4W, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy; D038761:Photobleaching; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000494:pharmacology*
chemical_list: D017319:Photosensitizing Agents; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D026082:Singlet Oxygen
keywords: HPPH-mediated PDT; PDT dose; cure index; fluence; in vivo mice study; mean [1O2]rx; photobleaching ratio