Photofrin-mediated Photodynamic Therapy Research Articles

Reactive Oxygen Species Explicit dosimetry for Pleural PDT

SignificancePreclinical studies show improved prediction of treatment outcome using [ROS]rx than light fluence rate or PDT dose. We demonstrate ROSED in a clinical setting. ApproachExplicit dosimetry of light fluence, photosensitizer concentration, and oxygen concentration is used to quantify the reactive oxygen species explicit dosimetry (ROSED) during Photofrin-mediated pleural PDT. Light fluence and photosensitizer concentration were measured by a customized multi-channel PDT dose dosimeter system. Diffuse correlation spectroscopy (DCS) contact probes were sutured to the pleural cavity wall after surgical resection of pleural mesothelioma tumor to monitor tissue blood flow (BFI) during intraoperative PDT treatment. Tissue oxygen concentration can be determined by utilizing tumor blood flow measured by DCS. ResultsLarge inter- and intra-patient heterogeneities in [ROS]rx were observed although an identical light dose of 60 J/cm2 was prescribed to all patients. ConclusionsThis study summarizes the current results of ROSED for a Phase II pleural PDT clinical trial.

Clinical PDT dose dosimetry for pleural Photofrin-mediated photodynamic therapy.

Photodynamic therapy (PDT) is an established cancer treatment utilizing light-activated photosensitizers (PS). Effective treatment hinges on the PDT dose-dependent on PS concentration and light fluence-delivered over time. We introduce an innovative eight-channel PDT dose dosimetry system capable of concurrently measuring light fluence and PS concentration during treatment. We aim to develop and evaluate an eight-channel PDT dose dosimetry system for simultaneous measurement of light fluence and PS concentration. By addressing uncertainties due to tissue variations, the system enhances accurate PDT dosimetry for improved treatment outcomes. The study positions eight isotropic detectors strategically within the pleural cavity before PDT. These detectors are linked to bifurcated fibers, distributing signals to both a photodiode and a spectrometer. Calibration techniques are applied to counter tissue-related variations and improve measurement accuracy. The fluorescence signal is normalized using the measured light fluence, compensating for variations in tissue properties. Measurements were taken in 78 sites in the pleural cavities of 20 patients. Observations reveal minimal Photofrin concentration variation during PDT at each site, juxtaposed with significant intra- and inter-patient heterogeneities. Across 78 treated sites in 20 patients, the average Photofrin concentration for all 78 sites is , with a median concentration of . The average PDT dose for all 78 sites is , with a median dose of . A significant variation in PDT doses is observed, with a maximum difference of 3.1 times among all sites within one patient and a maximum difference of 9.8 times across all patients. The introduced eight-channel PDT dose dosimetry system serves as a valuable real-time monitoring tool for light fluence and PS concentration during PDT. Its ability to mitigate uncertainties arising from tissue properties enhances dosimetry accuracy, thus optimizing treatment outcomes and bolstering the effectiveness of PDT in cancer therapy.

Fractionated Photofrin-Mediated Photodynamic Therapy Significantly Improves Long-Term Survival

This study investigates the effect of fractionated (two-part) PDT on the long-term local control rate (LCR) using the concentration of reactive oxygen species ([ROS]rx) as a dosimetry quantity. Groups with different fractionation schemes are examined, including a 2 h interval between light delivery sessions to cumulative fluences of 135, 180, and 225 J/cm2. While the total treatment time remains constant within each group, the division of treatment time between the first and second fractionations are explored to assess the impact on long-term survival at 90 days. In all preclinical studies, Photofrin is intravenously administered to mice at a concentration of 5 mg/kg, with an incubation period between 18 and 24 h before the first light delivery session. Fluence rate is fixed at 75 mW/cm2. Treatment ensues via a collimated laser beam, 1 cm in diameter, emitting light at 630 nm. Dosimetric quantities are assessed for all groups along with long-term (90 days) treatment outcomes. This study demonstrated a significant improvement in long-term survival after fractionated treatment schemes compared to single-fraction treatment, with the optimal 90-day survival increasing to 63%, 86%, and 100% vs. 20%, 25%, and 50%, respectively, for the three cumulative fluences. The threshold [ROS]rx for the optimal scheme of fractionated Photofrin-mediated PDT, set at 0.78 mM, is significantly lower than that for the single-fraction PDT, at 1.08 mM.

A Monte Carlo simulation for Moving Light Source in Intracavity PDT.

We developed a simulation method for modeling the light fluence delivery in intracavity Photodynamic Therapy (icav-PDT) for pleural lung cancer using a moving light source. Due to the large surface area of the pleural lung cavity, the light source needs to be moved to deliver a uniform dose around the entire cavity. While multiple fixed detectors are used for dosimetry at a few locations, an accurate simulation of light fluence and fluence rate is still needed for the rest of the cavity. We extended an existing Monte Carlo (MC) based light propagation solver to support moving light sources by densely sampling the continuous light source trajectory and assigning the proper number of photon packages launched along the way. The performance of Simphotek GPU CUDA-based implementation of the method - PEDSy-MC - has been demonstrated on a life-size lung-shaped phantom, custom printed for testing icav-PDT navigation system at the Perlman School of Medicine (PSM) - calculations completed under a minute (for some cases) and within minutes have been achieved. We demonstrate results within a 5% error of the analytic solution for multiple detectors in the phantom. PEDSy-MC is accompanied by a dose-cavity visualization tool that allows real-time inspection of dose values of the treated cavity in 2D and 3D, which will be expanded to ongoing clinical trials at PSM. PSM has developed a technology to measure 8-detectors in a pleural cavity phantom using Photofrin-mediated PDT that has been used during validation.

Evaluation of Fractionated Photofrin-mediated Photodynamic Therapy Using Different Light Fluences with Reactive Oxygen Species Explicit Dosimetry (ROSED).

Photodynamic therapy (PDT) is an established modality for cancer treatment, and reactive oxygen species explicit dosimetry (ROSED), based on direct measurements of in-vivo light fluence (rate), in-vivo photofrin concentration, and tissue oxygenation concentration, has been proved to provide the best dosimetric quantity which can be used to predict non-fractionated PDT outcome. This study performed ROSED for Photofrin-mediated PDT for mice bearing radiation-induced fibrosacorma (RIF) tumor. As demonstrated by our previous study, fractionated PDT with a 2-hour time interval can significantly improve the long-term cure rate (from 15% to 65% at 90 days), and it tends to increase as the light dose for the first light fraction gets larger. This study focused on further improving the long-term cure rate without introducing apparent toxicity using combinations of different first light fraction lengths and total light fluences. Photofrin was injected through the mouse tail vein at a concentration of 5 mg/kg. After 18~24 hours, treatment was delivered with a collimated laser beam of 1 cm diameter at 630 nm. Mice were treated using two fractions of light fluences with a 2-hour dark interval. Different dose metrics were quantified, including light fluence, PDT dose, and [ROS]rx. In addition, the total reacted [ROS]rx and treatment outcomes were evaluated and compared to identify the optimal light fraction length and total light fluence.

Multispectral singlet oxygen luminescent dosimetry (MSOLD) for Photofrin-mediated Photodynamic Therapy.

Direct detection of singlet-state oxygen ([1O2]) constitutes the holy grail dosimetric method for type II PDT, a goal that can be quantified using multispectral singlet oxygen dosimetry (MSOLD). However, the short lifetime and extremely weak nature of the singlet oxygen signal produced has given rise to a need to improve MSOLD signal-to-noise ratio. This study examines methods for optimizing MSOLD signal acquisition, specifically employing an orthogonal arrangement between detection and PDT treatment light, consisting of two fiber optics - connected to a 632-nm laser and an InGaAs detector respectively. Light collected by the InGaAs detector is then passed through a filter wheel, where spectral emission measurements are taken at 1200 nm, 1240 nm, 1250 nm, 1270 nm, and 1300 nm. The data, after fitting to the fluorescence background and a gaussian-fit for the singlet oxygen peak, is established for the background-subtracted singlet oxygen emission signal. The MSOLD signal is then compared with the singlet oxygen explicit dosimetry (SOED) results, based on direct measurements of in-vivo light fluence (rate), in-vivo Photofrin concentration, and tissue oxygenation concentration. This study focuses on validating the sensitivity and minimum detectability of MSOLD signal in various in-vitro conditions. Finally, the MSOLD device will be tested in Photofrin-mediated PDT for mice bearing Radiation-Induced Fibrosarcoma (RIF) tumors.

Evaluation of Detector Position and Light Fluence Distribution Using an Infrared Navigation System during Pleural Photodynamic Therapy†.

Photodynamic therapy (PDT) has been used to treat malignant pleural mesothelioma. Current practice involves delivering light to a prescribed light fluence with a point source, monitored by eight isotropic detectors inside the pleural cavity. An infrared (IR) navigation system was used to track the location of the point source throughout the treatment. The recorded data were used to reconstruct the pleural cavity and calculate the light fluence to the whole cavity. An automatic algorithm was developed recently to calculate the detector positions based on recorded data within an hour. This algorithm was applied to patient case studies and the calculated results were compared to the measured positions, with an average difference of 2.5 cm. Calculated light fluence at calculated positions were compared to measured values. The differences between the calculated and measured light fluence were within 14% for all cases, with a fixed scattering constant and a dual correction method. Fluence-surface histogram (FSH) was calculated for photofrin-mediated PDT to be able to cover 80% of pleural surface area to 50 J cm-2 (83.3% of 60 J cm-2 ). The study demonstrates that it will be possible to eliminate the manual measurement of the detector positions, reducing the patient's time under anesthesia.

Reactive oxygen species explicit dosimetry (ROSED) for fractionated photofrin-mediated photodynamic therapy (PDT).

Photodynamic therapy (PDT) is an established modality for cancer treatment and reactive oxygen species explicit dosimetry (ROSED), based on direct measurements of in-vivo light fluence (rate), in-vivo photofrin concentration, and tissue oxygenation concentration, has been proved to be an effective dosimetric quantity which can be used to predict PDT outcome. In this study, ROSED was performed for photofrin-mediated PDT for mice bearing radiation-induced fibrosacorma (RIF) tumor. PDT treatments were performed using single or fractionated illumination to a same total fluence of 135 Jcm-2. The effects of light fractionation on the total reacted [ROS]rx and treatment outcomes were evaluated.

Validation of multispectral singlet oxygen luminescence dosimetry (MSOLD) for photofrin-mediated photodynamic therapy.

Accurate dosimetry is crucial for the ongoing development and clinical study of photodynamic therapy (PDT). Current dosimetry standards range from less accurate methods involving measurement of only light fluence and photosensitizer concentration during treatment, to significantly improved methods such as singlet oxygen explicit dosimetry (SOED), a macroscopic model that includes an additional important parameter in its dosimetric calculations: ground-state oxygen concentration ([3O2]). However, neither of these models is a method of direct dosimetry. Multispectral singlet oxygen luminescence dosimetry (MSOLD) shows promise in this regard but requires significant improvement in signal quality and remains to be validated in a clinical setting. In this study, we validate a linearly increasing MSOLD signal with an InGaAs photodiode detector for increasing concentration (0 mg/kg to 200 mg/kg) in tissue-simulating phantoms containing photofrin, calculating a calibration curve based on 1270 nm peak-intensity signal and area under the curve for background-subtracted singlet oxygen emission. Additionally, we validate MSOLD against the current clinical dosimetry standard, SOED, through simultaneous measurement of SOED parameters and MSOLD signal for varying concentrations (50 μM - 300 μM). Finally, we investigate the effects of using very high gain amplification on InGaAs photodiode detectors to amplify the MSOLD signal for use in clinical models. We show that a calibration curve relating photosensitizer concentration (PS) and MSOLD signal can be established. Additionally, we demonstrate good correlation between MSOLD signal and SOED-calculated [1O2]rx. However, we show that when using high amplification on InGaAs photodiodes for long illumination times, the inherent instability in these detectors becomes apparent.

Reactive oxygen species explicit dosimetry to predict local tumor growth for Photofrin-mediated photodynamic therapy.

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∕cm2) and ϕ (75 or 150 mW∕cm2), tumor regrowth rate, k, was determined for each condition by fitting the tumor volume versus time to V0 *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/kctr , 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.

1O2 determined from the measured PDT dose and 3O2 predicts long-term response to Photofrin-mediated PDT

Photodynamic therapy (PDT) that employs the photochemical interaction of light, photosensitizer and oxygen is an established modality for the treatment of cancer. However, dosimetry for PDT is becoming increasingly complex due to the heterogeneous photosensitizer uptake by the tumor, and complicated relationship between the tissue oxygenation ([3O2]), interstitial light distribution, photosensitizer photobleaching and PDT effect. As a result, experts argue that the failure to realize PDT’s true potential is, at least partly due to the complexity of the dosimetry problem. In this study, we examine the efficacy of singlet oxygen explicit dosimetry (SOED) based on the measurements of the interstitial light fluence rate distribution, changes of [3O2] and photosensitizer concentration during Photofrin-mediated PDT to predict long-term control rates of radiation-induced fibrosarcoma tumors. We further show how variation in tissue [3O2] between animals induces variation in the treatment response for the same PDT protocol. PDT was performed with 5 mg kg−1 Photofrin (a drug-light interval of 24 h), in-air fluence rates (ϕair) of 50 and 75 mW cm−2 and in-air fluences from 225 to 540 J cm−2. The tumor regrowth was tracked for 90 d after the treatment and Kaplan–Meier analyses for local control rate were performed based on a tumor volume ⩽100 mm3 for the two dosimetry quantities of PDT dose and SOED. Based on the results, SOED allowed for reduced subject variation and improved treatment evaluation as compared to the PDT dose.

Porfimer sodium-mediated photodynamic therapy in patients with head and neck squamous cell carcinoma.

Photodynamic therapy is a less invasive therapeutic procedure for carcinomas. The goal of this study was to evaluate the utility of Photofrin (porfimer sodium)-mediated photodynamic therapy in patients with head and neck squamous cell carcinoma. Forty-two head and neck squamous cell carcinoma patients who underwent Photofrin-mediated photodynamic therapy were treated by intraoperative light activation at 630 nm via a fiber optic microlens, 48 h after injection. We evaluated the impact of age, sex, tumor stage, primary site, light dose, and cancer history on overall survival using a Cox proportional hazards model. Information on the survival status of patients was obtained after a mean follow-up period of 51 months (range, 6-180 months). The 5-year overall survival for all patients was 57.8 % (95 % confidence interval of the survival rate: 39.8 %-72.1 %). The complete response rate was 69.0 %, and the efficacy (complete response + partial response) was 97.6 %. Earlier tumor stage was associated with increased survival (p = 0.012). Diseases of the respiratory tract also showed significant association with survival as compared to those of the alimentary tract (p = 0.01). Photofrin-mediated photodynamic therapy is useful for treating head and neck squamous cell carcinomas, and provides an improved quality of life in patients with recurrent or residual disease.

Reactive oxygen species explicit dosimetry to predict local tumor control for Photofrin-mediated photodynamic therapy.

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/cm2) and ϕ (50 - 150 mW/cm2), tumor regrowth rate, k, was determined for each condition by fitting the tumor volume vs. time to V0*exp(k*t). Treatment was delivered with a collimated laser beam of 1 cm diameter at 630 nm. Explicit dosimetry of initial tissue oxygen concentration, tissue optical properties, and Photofrin concentration was used to calculate [ROS]rx,cal. ϕ was determined for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. Tissue oxygenation is measured using an oxylite oxygen probe to throughout the treatment to calculate the measured [ROS]rx,mea. Cure index, CI = 1-k/k ctr , for tumor gowth up to 14 days were determined as an endpoint using five dose metrics: light fluence, PDT dose, and [ROS]rx,cal, and [ROS]rx,mea. PDT dose was defined as the product of the time-integral of photosensitizer concentration and ϕ at a 3 mm tumor depth. Preliminary studies show that [ROS]rx,mea best correlates with CI and is an effective dosimetric quantity that can predict treatment outcome.

Inhibition of Autophagy with Chloroquine Enhanced Sinoporphyrin Sodium Mediated Photodynamic Therapy-induced Apoptosis in Human Colorectal Cancer Cells.

To evaluate the antitumor effect of sinoporphyrin sodium mediated photodynamic therapy (DVDMS-PDT) against human colorectal cancer (CRC) and to investigate the role of autophagy in its effect.Shrunken cells, condensed nuclei and increased levels of cleaved caspase-3 and Bax were observed in DVDMS-PDT treated HCT116 cells, reminiscent of apoptosis. DVDMS-PDT showed better antitumor efficiency in HCT116 cells than Photofrin mediated photodynamic therapy (PF-PDT) both in vitro and in vivo. And DVDMS-PDT caused autophagic characteristics: double membrane autophagosome structures and changes in autophagy-related protein expression (ATG7, P62, Bcl-2 and LC3-Ⅱ). In addition, inhibition of autophagy by chloroquine (CQ) promoted apoptosis, suggesting a possible protective role of autophagy in DVDMS-PDT-treated HCT116 cells, which was proved by flow cytometry and western blotting. The results of xenograft mouse model showed markedly increased apoptosis and significantly reduced tumor size in DVDMS-PDT treated group than Control, and DVDMS-PDT exhibited better antitumor efficiency than PF-PDT. Further, no visible tumor was observed in the CQ+DVDMS-PDT group at the end of the xenograft mouse experiment, which confirmed the hypothesis that autophagy was protective to DVDMS-PDT treated HCT116 cells.Our findings suggest that DVDMS is a promising photosensitizer and the combined use of autophagy inhibitor can remarkably enhance the DVDMS-PDT mediated anti-cancer efficiency in HCT116 cells both in vitro and in vivo.

Modeling Epidermal Growth Factor Inhibitor-mediated Enhancement of Photodynamic Therapy Efficacy Using 3D Mesothelioma Cell Culture.

We have demonstrated that lung-sparing surgery with intraoperative photodynamic therapy (PDT) achieves remarkably extended survival for patients with malignant pleural mesothelioma (MPM). Nevertheless, most patients treated using this approach experience local recurrence, so it is essential to identify ways to enhance tumor response. We previously reported that PDT transiently activates EGFR/STAT3 in lung and ovarian cancer cells and inhibiting EGFR via erlotinib can increase PDT sensitivity. Additionally, we have seen higher EGFR expression associating with worse outcomes after Photofrin-mediated PDT for MPM, and the extensive desmoplastic reaction associated with MPM influences tumor phenotype and therapeutic response. Since extracellular matrix (ECM) proteins accrued during stroma development can alter EGF signaling within tumors, we have characterized novel 3D models of MPM to determine their response to erlotinib combined with Photofrin-PDT. Our MPM cell lines formed a range of acinar phenotypes when grown on ECM gels, recapitulating the locally invasive phenotype of MPM in pleura and endothoracic fascia. Using these models, we confirmed that EGFR inhibition increases PDT cytotoxicity. Together with emerging evidence that EGFR inhibition may improve survival of lung cancer patients through immunologic and direct cell killing mechanisms, these results suggest erlotinib-enhanced PDT may significantly improve outcomes for MPM patients.

Determination of optical properties, drug concentration, and tissue oxygenation in human pleural tissue before and after Photofrin-mediated photodynamic therapy.

PDT efficacy depends on the concentration of photosensitizer, oxygen, and light delivery in patient tissues. In this study, we measure the in-vivo distribution of important dosimetric parameters, namely the tissue optical properties (absorption μa (λ) and scattering μs ' (λ) coefficients), photofrin concentration (cphotofrin), blood oxygen saturation (%StO2), and total hemoglobin concentration (THC), before and after PDT. We characterize the inter- and intra-patient heterogeneity of these quantities and explore how these properties change as a result of PDT treatment. The result suggests the need for real-time dosimetry during PDT to optimize the treatment condition depending on the optical and physiological properties.

Oxidation of protein-bound methionine in Photofrin-photodynamic therapy-treated human tumor cells explored by methionine-containing peptide enrichment and quantitative proteomics approach

In Photofrin-mediated photodynamic therapy (PDT), cell fate can be modulated by the subcellular location of Photofrin. PDT triggers oxidative damage to target cells, including the methionine (Met) oxidation of proteins. Here, we developed a new Met-containing peptide enrichment protocol combined with SILAC-based quantitative proteomics, and used this approach to explore the global Met oxidation changes of proteins in PDT-treated epidermoid carcinoma A431 cells preloaded with Photofrin at the plasma membrane, ER/Golgi, or ubiquitously. We identified 431 Met-peptides corresponding to 302 proteins that underwent severe oxidation upon PDT and observed overrepresentation of proteins related to the cell surface, plasma membrane, ER, Golgi, and endosome under all three conditions. The most frequently oxidized Met-peptide sequence was “QAMXXMM-E/G/M-S/G-A/G/F-XG”. We also identified several hundred potential Photofrin-binding proteins using affinity purification coupled with LC-MS/MS, and confirmed the bindings of EGFR and cathepsin D with Photofrin. The enzyme activities of both proteins were significantly reduced by Photofrin-PDT. Our results shed light on the global and site-specific changes in Met-peptide oxidation among cells undergoing Photofrin-PDT-mediated oxidative stress originating from distinct subcellular sites, and suggest numerous potential Photofrin-binding proteins. These findings provide new insight into the molecular targets through which Photofrin-PDT has diverse effects on target cells.

A Comparison of Dose Metrics to Predict Local Tumor Control for Photofrin‐mediated Photodynamic Therapy

This preclinical study examines light fluence, photodynamic therapy (PDT) dose and "apparent reacted singlet oxygen," [1 O2 ]rx , to predict local control rate (LCR) for Photofrin-mediated PDT of radiation-induced fibrosarcoma (RIF) tumors. Mice bearing RIF tumors were treated with in-air fluences (50-250 J cm-2 ) and in-air fluence rates (50-150 mW cm-2 ) at Photofrin dosages of 5 and 15 mg kg-1 and a drug-light interval of 24 h using a 630-nm, 1-cm-diameter collimated laser. A macroscopic model was used to calculate [1 O2 ]rx and PDT dose based on in vivo explicit dosimetry of the drug concentration, light fluence and tissue optical properties. PDT dose and [1 O2 ]rx were defined as a temporal integral of drug concentration and fluence rate, and singlet oxygen concentration consumed divided by the singlet oxygen lifetime, respectively. LCR was stratified for different dose metrics for 74 mice (66 + 8 control). Complete tumor control at 14 days was observed for [1 O2 ]rx ≥ 1.1 mm or PDT dose ≥1200 μm J cm-2 but cannot be predicted with fluence alone. LCR increases with increasing [1 O2 ]rx and PDT dose but is not well correlated with fluence. Comparing dosimetric quantities, [1 O2 ]rx outperformed both PDT dose and fluence in predicting tumor response and correlating with LCR.

A summary of light dose distribution using an IR navigation system for Photofrin-mediated Pleural PDT.

Uniform delivery of light fluence is an important goal for photodynamic therapy. We present summary results for an infrared (IR) navigation system to deliver light dose uniformly during intracavitory PDT by tracking the movement of the light source and providing real-time feedback on the light fluence rate on the entire cavity surface area. In the current intrapleural PDT protocol, 8 detectors placed in selected locations in the pleural cavity monitor the light doses. To improve the delivery of light dose uniformity, an IR camera system is used to track the motion of the light source as well as the surface contour of the pleural cavity. A MATLAB-based GUI program is developed to display the light dose in real-time during PDT to guide the PDT treatment delivery to improve the uniformity of the light dose. A dualcorrection algorithm is used to improve the agreement between calculations and in-situ measurements. A comprehensive analysis of the distribution of light fluence during PDT is presented in both phantom conditions and in clinical cases.

Dosimetry study of PHOTOFRIN-mediated photodynamic therapy in a mouse tumor model.

It is well known in photodynamic therapy (PDT) that there is a large variability between PDT light dose and therapeutic outcomes. An explicit dosimetry model using apparent reacted 1O2 concentration ([1O2]rx) has been developed as a PDT dosimetric quantity to improve the accuracy of the predicted ability of therapeutic efficacy. In this study, this explicit macroscopic singlet oxygen model was adopted to establish the correlation between calculated reacted [1O2]rx and the tumor growth using Photofrin-mediated PDT in a mouse tumor model. Mice with radiation-induced fibrosarcoma (RIF) tumors were injected with Photofrin at a dose of 5 mg/kg. PDT was performed 24h later with different fluence rates (50, 75 and 150 mW/cm2) and different fluences (50 and 135 J/cm2) using a collimated light applicator coupled to a 630nm laser. The tumor volume was monitored daily after PDT and correlated with the total light fluence and [1O2]rx. Photophysical parameters as well as the singlet oxygen threshold dose for this sensitizer and the RIF tumor model were determined previously. The result showed that tumor growth rate varied greatly with light fluence for different fluence rates while [1O2]rx had a good correlation with the PDT-induced tumor growth rate. This preliminary study indicated that [1O2]rx could serve as a better dosimetric predictor for predicting PDT outcome than PDT light dose.