Evaluation of singlet oxygen explicit dosimetry for predicting treatment outcomes of benzoporphyrin derivative monoacid ring A-mediated photodynamic therapy

Abstract

, "Evaluation of singlet oxygen explicit dosimetry for predicting treatment outcomes of benzoporphyrin derivative monoacid ring A-mediated photodynamic therapy," J. Biomed. Opt. Abstract. Existing dosimetric quantities do not fully account for the dynamic interactions between the key components of photodynamic therapy (PDT) or the varying PDT oxygen consumption rates for different fluence rates. Using a macroscopic model, reacted singlet oxygen (½ 1 O 2 rx ) was calculated and evaluated for its effectiveness as a dosimetric metric for PDT outcome. Mice bearing radiation-induced fibrosarcoma tumors were treated with benzoporphyrin derivative monoacid ring A (BPD) at a drug-light interval of 3 h with various in-air fluences (30 to 350 J∕cm 2 ) and in-air fluence rates (50 to 150 mW∕cm 2 ). Explicit measurements of BPD concentration and tissue optical properties were performed and used to calculate ½ 1 O 2 rx , photobleaching ratio, and PDT dose. For four mice, in situ measurements of 3 O 2 and BPD concentration were monitored in real time and used to validate the in-vivo photochemical parameters. Changes in tumor volume following treatment were used to determine the cure index, CI ¼ 1 − k∕k ctr , where k and k ctr are the tumor regrowth rates with PDT and without PDT, respectively. The correlation between CI and the dose metrics showed that the calculated ½ 1 O 2 rx at 3 mm is an effective dosimetric quantity for predicting treatment outcome and a clinically relevant tumor regrowth endpoint.

Reactive Oxygen Species Explicit Dosimetry for Photofrin‐mediated Pleural Photodynamic Therapy

“…Our group has demonstrated the feasibility of clinical PDT dose dosimetry by concurrent measurement of light fluence rate and photosensitizer concentration during PDT. In preclinical investigations, [ROS]rx, or [ 1 O 2 ]rx for type‐II PDT only, have been demonstrated to be the best dose metric to predict PDT treatment outcome ; however, its clinical implementation is challenging due to a lack of FDA‐approved instrument to measure tissue oxygenation reliably during PDT.…”

“…Since both photochemical consumption of oxygen and microvascular shutdown can lead to tissue hypoxia during PDT, ROS produced via the interactions of all three PDT inputs is the best dose metric for prediction of treatment outcomes. ROS effectively accounts for temporal changes in the light, photosensitizer and tissue oxygen during PDT (5)(6)(7)(8)(9)(10)(11)(12). Direct measurement of ROS, however, is very challenging in clinical settings due to the extremely weak signal and the short lifetime of ROS (13)(14)(15).…”

Light Sources and Dosimetry Techniques for Photodynamic Therapy

“…To perform explicit dosimetry, the concentration of photosensitizer, ground state oxygen, and the delivered light dose must be known. Practically, explicit dosimetry has been performed in preclinical studies with modeled ground state oxygen and measured photosensitizer concentration using fluorescence (94,(96)(97)(98)(99)(100).…”

Reactive oxygen species explicit dosimetry (ROSED) of a type 1 photosensitizer

“…An empirical reactive singlet oxygen explicit dosimetry (ROSED) model has been developed to calculate ROS (including 1 O 2 ) based on the temporal and spatial distribution of light fluence rate ( ϕ ), photosensitizer concentration ([S 0 ]), and tissue oxygenation uptakes ([ 3 O 2 ]) 2,8 . Several in vivo mouse studies have been performed using type II photosensitizers, (Photofrin 9,10 , HPPH 11,12 and BPD 13,14 ) and ROSED calculated [ 1 O 2 ] rx values were found to be correlated well with PDT outcomes. The validity of the ROSED in predicting treatment outcome of a type I PDT has not been established.…”