Interstitial Photodynamic Therapy Research Articles

Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model.

Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose-response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30 J/cm2.

Photodynamic Therapy of Non-Small Cell Lung Cancer. Narrative Review and Future Directions.

Photodynamic therapy (PDT) is an established treatment modality for non-small cell lung cancer. Phototoxicity, the primary adverse event, is expected to be minimized with the introduction of new photosensitizers that have shown promising results in phase I and II clinical studies. Early-stage and superficial endobronchial lesions less than 1 cm in thickness can be effectively treated with external light sources. Thicker lesions and peripheral lesions may be amenable to interstitial PDT, where the light is delivered intratumorally. The addition of PDT to standard-of-care surgery and chemotherapy can improve survival and outcomes in patients with pleural disease. Intraoperative PDT has shown promise in the treatment of non-small cell lung cancer with pleural spread. Recent preclinical and clinical data suggest that PDT can increase antitumor immunity. Crosslinking of signal transducer and activator of transcription-3 molecules is a reliable biomarker to quantify the photoreaction induced by PDT. Randomized studies are required to test the prognosis value of this biomarker, obtain approval for the new photosensitizers, and test the potential efficacy of interstitial and intraoperative PDT in the treatment of patients with non-small cell lung cancer.

Interstitial photodynamic therapy: Light fractionation effects on a preclinical model of glioblastoma

s / Photodiagnosis and Photodynamic Therapy 12 (2015) 325–375 347 natural (sunlight) light sources. Fluorescence imageswere taken to locate the distribution of the curcumin in themosquito larvae. Both curcumins derivative exhibited photoactivity, reaching 100% larval mortality after exposure to different light sources shown above. http://dx.doi.org/10.1016/j.pdpdt.2015.07.087 Study of ALA andMALmixtures in pig skin: PpIX production Alessandra Keiko Lima Fujita, Priscila Fernanda Campos de Menezes, Phamilla Gracielli Sousa Rodrigues, Michelle Barreto Requena, Cristina Kurachi, Andre Escobar, Rozana Wendler da Rocha, Andrigo Barboza de Nardi, Vanderlei S. Bagnato Sao Carlos Institute of Physics, University of Sao Paulo, Brazil Topical PDT using ALA (aminolevulinic acid) or methyl-ALA (MAL) as precursor of protoporphyrin IX (PpIX) shows some limitations. ALA is more hydrophilic than MAL, resulting in differences at the molecule interaction with the cells. The goal of study is evaluated the optimization of topical PDTusingALA andMAL in differentmixtures. This studywas done in vivo in porcine skinmodels using 7 categories of ALA andMALmixtures. The cream in different mixtures was applied and an occlusive dressing was placed. PpIX production in a porcine skin model was monitored using widefield fluorescence imaging and fluorescence spectroscopy collected at skin surface until 5 h of treatment. Seven types of mixture were tested, from 0 to 100% combinations, varying on 20%. The imaging analyses, showed the best results in PpIX productionwithmixtures from 40% to 80% of ALA. Both fluorescence techniques showed that the higher relative production of PpIX was present when the ALA concentration was of 40–80%. The investigation of the PpIX production as a function of the tissue depth is being performed. These results can be useful in Clinical Applications of PDT using topical ALA and M-ALA (Financial support: CNPq). http://dx.doi.org/10.1016/j.pdpdt.2015.07.088 Interstitial photodynamic therapy: Light fractionation effects on a preclinical model of glioblastoma Henri-Arthur Leroy, Maximilien Vermandel, Bertrand Leroux, Serge Mordon, Nicolas Reyns INSERM U1189 – ONCO-THAI Lille, Department of Neurosurgery/University Hospital, University of Lille,

Study of ALA and MAL mixtures in pig skin: PpIX production

s / Photodiagnosis and Photodynamic Therapy 12 (2015) 325–375 347 natural (sunlight) light sources. Fluorescence imageswere taken to locate the distribution of the curcumin in themosquito larvae. Both curcumins derivative exhibited photoactivity, reaching 100% larval mortality after exposure to different light sources shown above. http://dx.doi.org/10.1016/j.pdpdt.2015.07.087 Study of ALA andMALmixtures in pig skin: PpIX production Alessandra Keiko Lima Fujita, Priscila Fernanda Campos de Menezes, Phamilla Gracielli Sousa Rodrigues, Michelle Barreto Requena, Cristina Kurachi, Andre Escobar, Rozana Wendler da Rocha, Andrigo Barboza de Nardi, Vanderlei S. Bagnato Sao Carlos Institute of Physics, University of Sao Paulo, Brazil Topical PDT using ALA (aminolevulinic acid) or methyl-ALA (MAL) as precursor of protoporphyrin IX (PpIX) shows some limitations. ALA is more hydrophilic than MAL, resulting in differences at the molecule interaction with the cells. The goal of study is evaluated the optimization of topical PDTusingALA andMAL in differentmixtures. This studywas done in vivo in porcine skinmodels using 7 categories of ALA andMALmixtures. The cream in different mixtures was applied and an occlusive dressing was placed. PpIX production in a porcine skin model was monitored using widefield fluorescence imaging and fluorescence spectroscopy collected at skin surface until 5 h of treatment. Seven types of mixture were tested, from 0 to 100% combinations, varying on 20%. The imaging analyses, showed the best results in PpIX productionwithmixtures from 40% to 80% of ALA. Both fluorescence techniques showed that the higher relative production of PpIX was present when the ALA concentration was of 40–80%. The investigation of the PpIX production as a function of the tissue depth is being performed. These results can be useful in Clinical Applications of PDT using topical ALA and M-ALA (Financial support: CNPq). http://dx.doi.org/10.1016/j.pdpdt.2015.07.088 Interstitial photodynamic therapy: Light fractionation effects on a preclinical model of glioblastoma Henri-Arthur Leroy, Maximilien Vermandel, Bertrand Leroux, Serge Mordon, Nicolas Reyns INSERM U1189 – ONCO-THAI Lille, Department of Neurosurgery/University Hospital, University of Lille,

The effectivity of ALA-PDT using IPL evaluated by image and histological analysis using porcine skin models in vivo

s / Photodiagnosis and Photodynamic Therapy 12 (2015) 325–375 347 natural (sunlight) light sources. Fluorescence imageswere taken to locate the distribution of the curcumin in themosquito larvae. Both curcumins derivative exhibited photoactivity, reaching 100% larval mortality after exposure to different light sources shown above. http://dx.doi.org/10.1016/j.pdpdt.2015.07.087 Study of ALA andMALmixtures in pig skin: PpIX production Alessandra Keiko Lima Fujita, Priscila Fernanda Campos de Menezes, Phamilla Gracielli Sousa Rodrigues, Michelle Barreto Requena, Cristina Kurachi, Andre Escobar, Rozana Wendler da Rocha, Andrigo Barboza de Nardi, Vanderlei S. Bagnato Sao Carlos Institute of Physics, University of Sao Paulo, Brazil Topical PDT using ALA (aminolevulinic acid) or methyl-ALA (MAL) as precursor of protoporphyrin IX (PpIX) shows some limitations. ALA is more hydrophilic than MAL, resulting in differences at the molecule interaction with the cells. The goal of study is evaluated the optimization of topical PDTusingALA andMAL in differentmixtures. This studywas done in vivo in porcine skinmodels using 7 categories of ALA andMALmixtures. The cream in different mixtures was applied and an occlusive dressing was placed. PpIX production in a porcine skin model was monitored using widefield fluorescence imaging and fluorescence spectroscopy collected at skin surface until 5 h of treatment. Seven types of mixture were tested, from 0 to 100% combinations, varying on 20%. The imaging analyses, showed the best results in PpIX productionwithmixtures from 40% to 80% of ALA. Both fluorescence techniques showed that the higher relative production of PpIX was present when the ALA concentration was of 40–80%. The investigation of the PpIX production as a function of the tissue depth is being performed. These results can be useful in Clinical Applications of PDT using topical ALA and M-ALA (Financial support: CNPq). http://dx.doi.org/10.1016/j.pdpdt.2015.07.088 Interstitial photodynamic therapy: Light fractionation effects on a preclinical model of glioblastoma Henri-Arthur Leroy, Maximilien Vermandel, Bertrand Leroux, Serge Mordon, Nicolas Reyns INSERM U1189 – ONCO-THAI Lille, Department of Neurosurgery/University Hospital, University of Lille,

Treatment plan evaluation for interstitial photodynamic therapy in a mouse model by Monte Carlo simulation with FullMonte

Monte Carlo (MC) simulation is recognized as the “gold standard” for biophotonic simulation, capturing all relevant physics and material properties at the perceived cost of high computing demands. Tetrahedral-mesh-based MC simulations particularly are attractive due to the ability to refine the mesh at will to conform to complicated geometries or user-defined resolution requirements. Since no approximations of material or light-source properties are required, MC methods are applicable to the broadest set of biophotonic simulation problems. MC methods also have other implementation features including inherent parallelism, and permit a continuously-variable quality-runtime tradeoff. We demonstrate here a complete MC-based prospective fluence dose evaluation system for interstitial PDT to generate dose-volume histograms on a tetrahedral mesh geometry description. To our knowledge, this is the first such system for general interstitial photodynamic therapy employing MC methods and is therefore applicable to a very broad cross-section of anatomy and material properties. We demonstrate that evaluation of dose-volume histograms is an effective variance-reduction scheme in its own right which greatly reduces the number of packets required and hence runtime required to achieve acceptable result confidence. We conclude that MC methods are feasible for general PDT treatment evaluation and planning, and considerably less costly than widely believed.

Multifunctional ultrasmall nanoplatforms for vascular-targeted interstitial photodynamic therapy of brain tumors guided by real-time MRI

Photodynamic therapy (PDT) for brain tumors appears to be complementary to conventional treatments. A number of studies show the major role of the vascular effect in the tumor eradication by PDT. For interstitial PDT (iPDT) of brain tumors guided by real-time imaging, multifunctional nanoparticles consisting of a surface-localized tumor vasculature targeting neuropilin-1 (NRP-1) peptide and encapsulated photosensitizer and magnetic resonance imaging (MRI) contrast agents, have been designed. Nanoplatforms confer photosensitivity to cells and demonstrate a molecular affinity to NRP-1. Intravenous injection into rats bearing intracranial glioma exhibited a dynamic contrast-enhanced MRI for angiogenic endothelial cells lining the neovessels mainly located in the peripheral tumor. By using MRI completed by NRP-1 protein expression of the tumor and brain adjacent to tumor tissues, we checked the selectivity of the nanoparticles. This study represents the first in vivo proof of concept of closed-head iPDT guided by real-time MRI using targeted ultrasmall nanoplatforms. From the Clinical EditorThe authors constructed tumor vascular peptide targeting multifunctional silica-based nanoparticles, with encapsulated gadolinium oxide as MRI contrast agent and chlorin as a photosensitizer, as a proof of concept novel treatment for glioblastoma in an animal model.

Малоинвазивные методы в лечении больных раком предстательной железы

The incidence of prostate cancer has increased in recent decades. Radical prostatectomy and radiotherapy are the standard methods of radical treatment of patients with prostate cancer. The complications and reduced quality of life of patients often develop after radical treatment. These facts were the basis for the search and implementation of new minimally invasive treatments. Effective treatment of patients and reduce the number of complications there are goals of minimally invasive treatments. Information about modern methods of minimally invasive treatment of patients with prostate cancer, such as cryosurgical ablation, high-intensity focused ultrasound therapy is presented in this article. Furthermore, mechanisms of action, the process of treatment, oncological efficacy and possible complications are described. The article includes information on the experimental methods, such as interstitial thermotherapy and photodynamic therapy. International studies of use of these methods are given. In addition, the method electrochemical lysis is shown in this article, the results of clinical practice in patients with prostate cancer. Key words Prostate cancer, minimally invasive treatments, electrochemical lysis

Photodynamic therapy in the treatment of intracranial gliomas: A review of current practice and considerations for future clinical directions

Invasive grade III and IV malignant gliomas remain difficult to treat with a typical survival time post-diagnosis hovering around 16 months with only minor extension thereof seen in the past decade, whereas some improvements have been obtained towards five-year survival rates for which completeness of resection is a prerequisite. Optical techniques such as fluorescence guided resection (FGR) and photodynamic therapy (PDT) are promising adjuvant techniques to increase the tumor volume reduction fraction. PDT has been used in combination with surgical resection or alternatively as standalone treatment strategy with some success in extending the median survival time of patients compared to surgery alone and the current standard of care. This document reviews the outcome of past clinical trials and highlights the general shift in PDT therapeutic approaches. It also looks at the current approaches for interstitial PDT and research options into increasing PDT's glioma treatment efficacy through exploiting both physical and biological-based approaches to maximize PDT selectivity and therapeutic index, particularly in brain adjacent to tumor (BAT). Potential reasons for failing to demonstrate a significant survival advantage in prior PDT clinical trials will become evident in light of the improved understanding of glioma biology and PDT dosimetry.

Laser Diode System For Interstitial Photodynamic Therapy

Interstitial Photodynamic Therapy (IPDT) is a promising form of treatment of deep-seated and bulky malignant tumors, based on the lethal cell response to the photochemical reactions when drug is light activated at presence of oxygen. After intravenous administration, the drug is retained selectively by malignant cells, and then, the light is delivered to the target tissue through multiple optical fibers. In order to accomplish an effective internal illumination, laser sources are preferably used because of two important reasons: the laser beam is easily focused to optical fibers, and the monochromatic light can be confined to the narrow absorption band of the drug. In this work we present the design of an irradiation laser system, which involves a 635nm laser diode and a delivering fiber system, for 5-ALA mediated IPDT.

Image-guided interstitial photodynamic therapy for squamous cell carcinomas: Preclinical investigation

ObjectivePhotodynamic therapy (PDT) is a clinically approved minimally invasive treatment for cancer. In this preclinical study, using an imaging-guided approach, we examined the potential utility of PDT in the management of bulky squamous cell carcinomas (SCCs). MethodsTo mimic bulky oropharyngeal cancers seen in the clinical setting, intramuscular SCCs were established in female C3H mice. Animals were injected with the photosensitizer, 2-[hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH; 0.4μmol/kg, i.v.) and tumors were illuminated 24h post injection with 665nm light. PDT as a single treatment modality was administered by surface illumination or by interstitial placement of fibers (iPDT). Magnetic resonance imaging was used to guide treatment and assess tumor response to PDT along with correlative histopathologic assessment. ResultsInterstitial HPPH-PDT resulted in a marked change on T2 maps 24h post treatment compared to untreated controls or transcutaneous illumination. Corresponding apparent diffusion coefficient maps also showed hyperintense areas in tumors following iPDT suggestive of effective photodynamic cell kill. Histologic sections (H&E) confirmed presence of extensive tumor necrosis following iPDT. ConclusionsThese results highlight the potential utility of PDT in the treatment of bulky oropharyngeal cancers. The findings of our study also demonstrate the utility of MRI as a non-invasive tool for mapping of early tissue response to PDT.

Comparison of flat cleaved and cylindrical diffusing fibers as treatment sources for interstitial photodynamic therapy

For interstitial photodynamic therapy (iPDT) of bulky tumors, careful treatment planning is required in order to ensure that a therapeutic dose is delivered to the tumor, while minimizing damage to surrounding normal tissue. In clinical contexts, iPDT has typically been performed with either flat cleaved or cylindrical diffusing optical fibers as light sources. Here, the authors directly compare these two source geometries in terms of the number of fibers and duration of treatment required to deliver a prescribed light dose to a tumor volume. Treatment planning software for iPDT was developed based on graphics processing unit enhanced Monte Carlo simulations. This software was used to optimize the number of fibers, total energy delivered by each fiber, and the position of individual fibers in order to deliver a target light dose (D90) to 90% of the tumor volume. Treatment plans were developed using both flat cleaved and cylindrical diffusing fibers, based on tissue volumes derived from CT data from a head and neck cancer patient. Plans were created for four cases: fixed energy per fiber, fixed number of fibers, and in cases where both or neither of these factors were fixed. When the number of source fibers was fixed at eight, treatment plans based on flat cleaved fibers required each to deliver 7180-8080 J in order to deposit 90 J/cm(2) in 90% of the tumor volume. For diffusers, each fiber was required to deliver 2270-2350 J (333-1178 J/cm) in order to achieve this same result. For the case of fibers delivering a fixed 900 J, 13 diffusers or 19 flat cleaved fibers at a spacing of 1 cm were required to deliver the desired dose. With energy per fiber fixed at 2400 J and the number of fibers fixed at eight, diffuser fibers delivered the desired dose to 93% of the tumor volume, while flat cleaved fibers delivered this dose to 79%. With both energy and number of fibers allowed to vary, six diffusers delivering 3485-3600 J were required, compared to ten flat cleaved fibers delivering 2780-3600 J. For the same number of fibers, cylindrical diffusers allow for a shorter treatment duration compared to flat cleaved fibers. For the same energy delivered per fiber, diffusers allow for the insertion of fewer fibers in order to deliver the same light dose to a target volume.

Abstract B148: Ultrasound image guided combination therapies involving photodynamic therapy and irinotecan.

Abstract Introduction: The field of cancer therapeutics is moving towards attacking the pathology with mechanistically distinct or synergistic combination therapies. In addition to possessing distinct cytotoxicity mechanisms, factors such as dose and sequence of combination therapy needs to be determined for effective therapeutic outcome. Non-invasive imaging techniques play a major role in personalizing these therapies by providing quantitative information on tumor volume, perfusion, oxygenation status, drug concentration etc. In particular we utilized ultrasound imaging to gauge the efficacy of photodynamic therapy (PDT) and irinotecan combination therapy in orthotopic pancreatic tumors of different volume. The rationale behind choosing PDT and irinotecan combination is that Irinotecan intracellular concentrations are increased, as PDT is known to cause destruction of ABC transporters that are responsible for the efflux of the drug and its metabolites outside of the cells. Photoacoustic imaging (a technique that provides contrast based on optical absorption properties of the tissue) was utilized to monitor changes in blood volume and oxygen saturation post photodynamic therapy. Materials and Methods: Orthotopic or subcutaneous pancreatic tumor models were established using MIA PaCA-2 cell line in Swiss Nu/Nu mice (4-6 weeks old). Cells (1 × 106in 50 μL of Matrigel-containing media) were injected into the pancreas or subcutaneously using a 301/2-gauge needle. Orthotopic tumors were imaged to gauge the combination treatment efficacy while the subcutaneous tumors provided change in tumor blood volume post PDT. Ultrasound imaging was used to non-invasively monitor tumor volume in mice and treatment was initiated when the tumors reached ∼35 mm3or ∼70 mm3. Irinotecan and photosensitizer, Benzoporphyrin derivative (BPD) were encapsulated in liposomes and injected via tail vein at concentrations 0.25 mg/kg and 20 mg/kg respectively, 60 minutes prior to PDT light irradiation. Interstitial PDT (690 nm laser, 100mW/cm2, 75 J/cm2) was performed on the exteriorized pancreas of the anesthetized mice with orthotopic tumors. Subcutaneous tumors also received the same PDT dose. Ultrasound and photoacoustic imaging was performed using commercially available Vevo LAZR system. Results and Conclusions: The longitudinal non-invasive ultrasound monitoring of orthotopic tumor volume in response to combination therapy was carried out with appropriate controls. We observed that PDT significantly enhances the tumoricidal efficacy of irinotecan and significantly inhibited tumor growth up to at least 3 weeks post-treatment (p < 0.05). A second combination treatment given at this point did not yield a reduction in tumor volume. In addition we also observed the treatment was ineffective in larger tumors. Photoacoustic imaging of subcutaneous tumors showed decrease in oxygen saturation and blood volume post PDT. The findings of this study recognize the importance of longitudinally monitoring tumor volume, vasculature and blood oxygen status for success of combination treatments. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B148. Citation Format: Srivalleesha Mallidi, Huang-Chiao Huang, Zhiming Mai, Ruth Goldschmidt, Joyce Liu, Patrick Chiang, Dmitriy Timerman, Imran Rizvi, Bryan Spring, Akilan Palanisami, Tayyaba Hasan. Ultrasound image guided combination therapies involving photodynamic therapy and irinotecan. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B148.

MR and CT based treatment planning for mTHPC mediated interstitial photodynamic therapy of head and neck cancer: Description of the method

Interstitial photodynamic therapy is a potentially important tool in the management of voluminous or deep-seated recurrent head and neck cancers. The described treatment algorithm in this manuscript consists of the treatment simulation, implantation of light sources, verification, modification of the treatment plan if necessary, and illumination. The tumor is delineated on imaging sections (CT, MRI, and/or PET/CT) and the treatment is simulated by virtually introducing light sources to the tumor volume on specially modified brachytherapy software. This enables us to determine if the treatment is technically feasible, and information about approximate number and location of light sources necessary. Following implantation of catheters in which the light sources will be introduced, CT or MR scan is performed to verify the actual location of the implanted catheters. The verification-CT is imported to the software and co-registered with pre-treatment images to observe the deviations from the simulation. The simulation is run again with the actual position of the light sources to determine if any additional light sources are necessary and adaptation of the source length in order to cover the tumor volume (modification). Thereafter the tumor is illuminated. This method has the potential to help with identifying iPDT feasible patients by simulating before the actual treatment. The suboptimal placement of light sources can be identified and corrected. The simulations were documented and saved for subsequent evaluation of the technique. The proposed technique can help standardize and document iPDT.

Strategies of airway management for head and neck photo‐dynamic therapy

Photodynamic therapy (PDT) is a minimally invasive treatment modality which has great clinical implications, especially in head and neck oncology. Post-operative swelling is a well-documented consequence of PDT. It is paramount the airway remains patent for these patients. A tracheostomy remains the gold standard treatment modality for base of tongue tumours susceptible to post operative PDT inflammation, which can lead to a compromised airway. We have carried out a retrospective study to outline the airway management strategies employed for head and neck cancer patients treated with PDT and suggest recommendations for future management. This retrospective clinical study utilises 88 patients (53 males and 35 females) treated at the UCLH Head and Neck Center, London (between 2006 and 2013), for treatment of various lesions with superficial and/or interstitial PDT, when the airway could potentially be compromised. Of the 88 patients selected 60 had interstitial PDT (iPDT) and 13 had superficial PDT (sPDT). Fifteen patients were treated with both iPDT and sPDT. Among the iPDT patients 19 had a trachestomy; two patients a Quicktrach; four a Cook Airway Exchange Catheter (CEAC); one a percutaneous tracheostomy; one a needle tracheostomy and 33 patients did not receive any temporary airway pathways. Among the sPDT patients two had a trachestomy. Although the majority of patients did not suffer any major incidents, one sPDT patient required an emergency tracheostomy two days post-operatively. Airway management is vital when planning PDT treatment for tongue based tumours. Consider a more conventional approach when the lesion being targeted is located at a higher risk site: Floor of mouth/posterior tongue/tongue base or when multiple oral sites are being treated.

SU‐E‐I‐88: Diffuse Optical Tomography for Characterization of Optical Properties in Interstitial PDT

Purpose: To characterize spatial distribution of optical properties (OP) for the interstitial photodynamic therapy (PDT) dosimetry using diffuse optical tomography (DOT). Methods: A spatial distribution of interstitial optical properties (absorption and reduced scattering coefficients) in a solid prostate phantom with OP heterogeneities was measured by scanning optical detector and source fibers with a multi‐channel motorized system. Several algorithms optimizing the scanning process were developed for the data acquisition system. The calculated light fluence rates were compared with measured ones to recover the heterogeneous optical properties. A mathematical phantom was used to test the reconstruction. Results: The ability to correctly separate absorption and scattering coefficients depended on the accuracy of the light fluence source measurement. The difference between measured and reconstructed fluence rates was within 10%. The DOT allowed reliable recovery of the absorption coefficients. Conclusion: The efficacy of PDT depends on the light distribution within the treated tissue. Since the spatial distribution of tissue optical properties affects the light distribution, the accurate determination of the OP spatial distribution is critical for the interstitial PDT treatment. This work is supported by the national Institute of Health (NIH) grants P01 CA87971 and R01 CA154562

Endoscopic Vascular Targeted Photodynamic Therapy with the Photosensitizer WST11 for Benign Prostatic Hyperplasia in the Preclinical Dog Model

Vascular targeted photodynamic therapy with WST11 (TOOKAD® Soluble) is in phase III clinical trials of an interstitial transperineal approach for focal therapy of prostate cancer. We investigated the safety and efficacy of the endourethral route in the context of benign prostatic hyperplasia in the dog model. An optical laser fiber was positioned in the prostatic urethra of 34 dogs, including 4 controls. It was connected to a 753 nm diode laser at 200 mW/cm fluence, delivering 200 to 300 J. WST11 (5 to 15 mg/kg) was infused intravenously in 2 modes, including continuous, starting 5 to 15 minutes before and during illumination, or a bolus 5 to 10 minutes before illumination. Prostate ultrasound, cystourethrogram, urodynamics and histopathology were performed. Followup was 1 week to 1 year. Endourethral WST11 vascular targeted photodynamic therapy was uneventful in all except 1 dog, which experienced urinary retention but reached the 1-week end point. All prostates except those in controls showed hemorrhagic lesions. They consisted of 2 levels of concentric alterations, including periurethral necrosis with endothelial layer destruction and adjacent inflammation/atrophy with normal blood vessels. Prostatic urethral width increased as early as 6 weeks after treatment, while prostatic volume decreased, reaching 25% by 18 to 26 weeks. A parallel decrease in urethral pressure at 6 weeks lasted up to 1 year. We confirmed the vascular effect of endourethral WST11 vascular targeted photodynamic therapy. To our knowledge we report for the first time that the resulting periurethral necrosis led to significant, sustained widening of the prostatic urethra, accompanied by long-term improvement in urodynamic parameters. These findings support future clinical applications of this minimally invasive approach to benign prostatic hyperplasia.

Protoporphyrin IX Fluorescence and Photobleaching During Interstitial Photodynamic Therapy of Malignant Gliomas for Early Treatment Prognosis

Interstitial photodynamic therapy (iPDT) of non-resectable recurrent glioblastoma using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has shown a promising outcome. It remained unclear, however, to what extent inter- and intra-tumoural differences of PpIX concentrations influence the efficacy of iPDT. In the current pilot study, we analysed PpIX concentrations quantitatively and assessed PpIX induced fluorescence and photobleaching intraoperatively. Five patients harbouring non-resectable glioblastomas were included. ALA (20 or 30 mg/kg body weight) was given 5-8 hours before treatment. Stereotactic biopsies were taken throughout the tumour volume for both histological analysis and determination of PpIX concentrations, which were measured by chemical extraction. Cylindrical light diffusors were stereotactically implanted. Prior to and after irradiation, fluorescence measurements were performed. Outcome measurement was based on clinical and neuro-radiological follow up. In three patients, a strong PpIX fluorescence was seen before treatment, which was completely photobleached after iPDT. High concentrations of PpIX could be detected in viable tumour parts of these patients (mean PpIX uptake per tumour: 1.4-3.0 µM). In the other two patients, however, no or only low PpIX uptake (0-0.6 µM) could be detected. The patients with strong PpIX uptake showed treatment response and long-term clinical stabilisation (no progression in 29, 30 and 36 months), early treatment failure was seen in the remaining two patients (death after 3 and 9 months). Intra-tumoural PpIX concentrations exhibited pronounced inter- and intra-tumoural variations in glioblastoma, which are directly linked to variable degrees of fluorescence intensity. High intra-tumoural PpIX concentrations with strong fluorescence intensity and complete photobleaching after iPDT seem to be associated with favourable outcome. Real-time monitoring of PpIX fluorescence intensity and photobleaching turned out to be feasible and safe and might be employed for early treatment prognosis of iPDT.

A robotic multi-channel platform for interstitial photodynamic therapy.

A custom-made robotic multichannel platform for interstitial photodynamic therapy (PDT) and diffuse optical tomography (DOT) was developed and tested in a phantom experiment. The system, which was compatible with the operating room (OR) environment, had 16 channels for independent positioning of light sources and/or isotropic detectors in separate catheters. Each channel's motor had an optical encoder for position feedback, with resolution of 1.5 mm, and a maximum speed of 5 cm/s. Automatic calibration of detector positions was implemented using an optical diode beam that defined the starting position of each motor, and by means of feedback algorithms controlling individual channels. As a result, the accuracy of zero position of 0.1 mm for all channels was achieved. We have also employed scanning procedures where detectors automatically covered the appropriate range around source positions. Thus, total scan time for a typical optical properties (OP) measurement throughout the phantom was about 1.5 minutes with point sources. The OP were determined based on the measured light fluence rates. These enhancements allow a tremendous improvement of treatment quality for a bulk tumor compared to the systems employed in previous clinical trials.

OC-037: mTHPC Mediated Interstitial Photodynamic Therapy of Recurrent Head and Neck Cancer: Development of a New Method

OC-037: mTHPC Mediated Interstitial Photodynamic Therapy of Recurrent Head and Neck Cancer: Development of a New Method