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

Abstract

Explicit dosimetry of treatment light fluence and implicit dosimetry of photosensitizer photobleaching are commonly used methods to guide dose delivery during clinical PDT. Tissue oxygen, however, is not routinely monitored intraoperatively even though it is one of the three major components of treatment. Quantitative information about in vivo tissue oxygenation during PDT is desirable, because it enables reactive oxygen species explicit dosimetry (ROSED) for prediction of treatment outcome based on PDT‐induced changes in tumor oxygen level. Here, we demonstrate ROSED in a clinical setting, Photofrin‐mediated pleural photodynamic therapy, by utilizing tumor blood flow information measured by diffuse correlation spectroscopy (DCS). A DCS contact probe was sutured to the pleural cavity wall after surgical resection of pleural mesothelioma tumor to monitor tissue blood flow (blood flow index) during intraoperative PDT treatment. Isotropic detectors were used to measure treatment light fluence and photosensitizer concentration. Blood‐flow‐derived tumor oxygen concentration, estimated by applying a preclinically determined conversion factor of 1.5 × 109 μMs cm−2 to the blood flow index, was used in the ROSED model to calculate the total reacted reactive oxygen species [ROS]rx. Seven patients and 12 different pleural sites were assessed and large inter‐ and intrapatient heterogeneities in [ROS]rx were observed although an identical light dose of 60 J cm−2 was prescribed to all patients.

Light Fluence Rate and Tissue Oxygenation (StO2) Distributions Within the Thoracic Cavity of Patients Receiving Intraoperative Photodynamic Therapy for Malignant Pleural Mesothelioma

“…Of further consideration is observed variations in tissue levels of the photosensitizer (Photofrin), also reported in the Ong et al contribution to this issue (27). Photofrin levels could vary substantially between subjects, as well as among tissues of the same patient, a finding not dissimilar from that previously reported (37,38).…”

“…Median values varied by more than twofold, from 31 to 70 mW cm −2 . Four subjects (17,18,20,27) could be classified as “low fluence rate (LFR)” subjects based on the criteria that the 75 th percentile value was <50 mW cm −2 for fluence rate measurements among tissue sites in each of these subjects. Contrastingly, subjects 3, 8, 14 32 and 37 could be classified as “intermediate fluence rate subjects (IFR)” based on the criteria that the 25 th percentile value was > 50 mW cm −2 for all tissue sites in these subjects.…”

“…In contrast to the association between pre-PDT S t O 2 and the PDT-induced change in S t O 2 , we did not find an association between treatment-averaged fluence rate and PDT effect on S t O 2 . Interestingly, in another report of this same issue of Photochemistry and Photobiology, Ong et al (27) demonstrate that tissue oxygenation, calculated from data on relative blood flow, fluctuates during light delivery for PDT of MPM in a manner that may associate with fluence rate. This report shows patterns of increasing and decreasing fluence rate that temporally associate with corresponding changes in tissue oxygenation and thus suggests that interactions between fluence rate and oxygenation may be detectable at the level of instantaneous light delivery to a tissue site.…”

In vivo Tissue Evaluation Reveals Improvements in Explicit PDT Dosimetry

“…The report of Cengel et al (1) forms part of a growing body of work not only using PDT as an adjuvant to surgery (29)(30)(31)(32)(33)(34)(35)(36)(37)(38), but also in advancing explicit PDT dosimetry (39,40). Their work stands as an important contribution in assessing tissue optical properties and oxygenation, and sensitizer effects in the peritoneal cavity.…”

“…The sensitizer used by Cengel et al (1) for longer wavelength absorption at 690 nm was BPD, as it has better light penetration depth than the 630 nm used for Photofrin. But there are still needs in this area, including improved sensitizer localization in the tumor (29,30). In the Cengel studies (1), the BPD concentration is obtained by diffuse fluorescence spectroscopy in each particular tissue.…”