Open AccessReactive oxygen species explicit dosimetry to predict local tumor growth for Photofrin-mediated photodynamic therapy
Author(s) -
Tianqi Sheng,
Yi Hong Ong,
Theresa M. Busch,
Timothy C. Zhu
Publication year - 2020
Publication title -
biomedical optics express
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.362
H-Index - 86
ISSN - 2156-7085
DOI - 10.1364/boe.393524
Subject(s) - photodynamic therapy , singlet oxygen , dosimetry , fluence , reactive oxygen species , oxygen , photosensitizer , fibrosarcoma , materials science , collimated light , chemistry , nuclear medicine , analytical chemistry (journal) , optics , laser , medicine , pathology , photochemistry , physics , biochemistry , organic chemistry , chromatography
Although photodynamic therapy (PDT) is an established modality for cancer treatment, current dosimetric quantities, such as light fluence and PDT dose, do not account for the differences in PDT oxygen consumption for different fluence rates ( ϕ ). A macroscopic model was adopted to calculate reactive oxygen species concentration ([ ROS ] rx ) to predict Photofrin-PDT outcome in mice bearing radiation-induced fibrosarcoma (RIF) tumors. Singlet oxygen is the primary cytotoxic species for ROS, which is responsible for cell death in type II PDT, although other type I ROS is included in the parameters used in our model. Using a combination of fluences (50-250 J∕cm 2 ) and ϕ (75 or 150 mW∕cm 2 ), tumor regrowth rate, k , was determined for each condition by fitting the tumor volume versus time to V 0 * exp(k * t) . Treatment was delivered with a collimated laser beam of 1 cm diameter at 630 nm. Explicit dosimetry of light fluence rate on tissue surface, tissue oxygen concentration, tissue optical properties, and Photofrin concentration were performed. Light fluence rate at 3 mm depth ( ϕ 3mm ) was determined for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. Initial tissue oxygenation [ 3 O 2 ] 0 was measured by an Oxylite oxygen probe before PDT and used to calculate [ ROS ] rx,calc. This value was compared to [ ROS ] rx,meas as calculated with the entire tissue oxygen spectrum [ 3 O 2 ](t), measured over the duration of light delivery for PDT. Cure index, CI = 1- k/k ctr , for tumor growth up to 14 days after PDT was predicted by four dose metrics: light fluence, PDT dose, and [ ROS ] rx,calc , and [ ROS ] rx,meas . PDT dose was defined as the product of the time-integral of photosensitizer concentration and ϕ at a 3 mm tumor depth. These studies show that [ ROS ] rx,meas best correlates with CI and is an effective dosimetric quantity that can predict treatment outcome.