Interstitial Photodynamic Therapy of the Canine Prostate Using Intra-Arterial Administration of Photosensitizer and Computerized Pulsed Light Delivery (original) (raw)
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Journal of Biomedical Optics, 2016
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 wholeprostate 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∕cm 2 .
The Journal of Urology, 2013
Purpose: Vascular targeted photodynamic therapy with WST11 (TOOKADÒ 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. Materials and Methods: 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. Results: 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. Conclusions: 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.
Lasers in Surgery and Medicine, 2005
Background and Objectives-Photodynamic therapy (PDT) mediated with Tookad (Pdbacteriopheophorbide, WST09) was investigated pre-clinically as part of a program to develop an alternative modality for treating prostate cancer. Study Design/Materials and Methods-Spontaneous canine prostate cancer and normal canine prostate were used as the animal models. Interstitial PDT was performed by IV infusion of the photosensitizer and irradiating the prostates with a diode laser (763 nm). The prostates were harvested 1-week post-PDT and subjected to histopathologic examinations. The effects of the drug doses and light doses were studied for one-and two-session PDT. Pharmacokinetics were studied using HPLC assay. The feasibility of using perfusing CT scans for assessing PDT lesions was also evaluated. Results-Tookad is a vascular-acting drug and clears rapidly from the circulation. Tookad-PDTinduced lesions, in both normal and cancerous prostates, were characterized by marked hemorrhagic necrosis. Conclusions-Tookad-PDT is very effective in ablating prostatic tissue through its vascular effects.
Photochemistry and Photobiology, 2007
Photodynamic therapy (PDT) uses light to activate a photosensitizer to achieve localized tumor control. In this study, PDT mediated by a second-generation photosensitizer, palladium-bacteriopheophorbide WST09 (Tookad) was investigated as an alternative therapy for prostate cancer. Normal canine prostate was used as the animal model. PDT was performed by irradiating the surgically exposed prostate superficially or interstitially at 763 nm to different total fluences (100 or 200 J/cm 2 ; 50, 100 or 200 J/cm) at 5 or 15 min after intravenous administration of the drug (2 mg/kg). Areas on the bladder and colon were also irradiated. The local light fluence rate and temperature were monitored by interstitial probes in the prostate. All animals recovered well, without urethral complications. During the 1 week to 3 month posttreatment period, the prostates were harvested for histopathological examination. The PDT-induced lesions showed uniform hemorrhagic necrosis and atrophy, were well delineated from the adjacent normal tissue and increased linearly in diameter with the logarithm of the delivered light fluence. A maximum PDT-induced lesion size of over 3 cm diameter could be achieved with a single interstitial treatment. There was no damage to the bladder or rectum caused by scattered light from the prostate. The bladder and rectum were also directly irradiated with PDT. At 80 J/cm 2 , a full-depth necrosis was observed but resulted in no perforation. At 40 J/cm 2 , PDT produced minimal damage to the bladder or rectum. On the basis of optical dosimetry, we have estimated that 20 J/cm 2 is the fluence required to produce prostatic necrosis. Thus, the normal structure adjacent to the prostate can be safely preserved with careful dosimetry. At therapeutic PDT levels, there was no structural or functional urethral damage even when the urethra was within the treated region. Hence, Tookad-PDT appears to be a promising candidate for prostate ablation in patients with recurrent, or possibly even primary, prostate cancer.
Photodynamic therapy in urology: What can we do now and where are we heading?
Photodiagnosis and Photodynamic Therapy, 2012
Background: Photodynamic therapy (PDT) is an innovative technique in oncologic urology. Its application appears increasingly realistic to all kind of cancers with technological progress made in treatment planning and light delivery associated with the emergence of novel photosensitizers. The aim of this study is to review applications of this technique in urology. Materials and methods: We reviewed the literature on PDT for urological malignancies with the following key words: photodynamic therapy, prostate cancer, kidney cancer, urothelial cancer, penile cancer and then by cross-referencing from previously identified studies. Results: Focal therapy of prostate cancer is an application of PDT. Clinical studies are ongoing to determine PDT efficacy and safety. PDT as salvage treatment after radiotherapy has been tested. Oncologic results were promising but important side effects were reported. Individual dosimetric planning is necessary to avoid toxicity.
Photochemistry and Photobiology, 2003
The optical properties (absorption [m a ], transport scattering [m 0 s ] and effective attenuation [m eff ] coefficients) of normal canine prostate were measured in vivo using interstitial isotropic detectors. Measurements were made at 732 nm before, during and after motexafin lutetium (MLu)-mediated photodynamic therapy (PDT). They were derived by applying the diffusion theory to the in vivo peak fluence rates measured at several distances (3, 6, 9, 12 and 15 mm) from the central axis of a 2.5 cm cylindrical diffusing fiber (CDF). m a and m 0 s varied between 0.03-0.58 and 1.0-20 cm 21 , respectively. m a was proportional to the concentration of MLu. m eff varied between 0.33 and 4.9 cm 21 (mean 1.3 6 1.1 cm 21 ), corresponding to an optical penetration depth (d 5 1/m eff ) of 0.5-3 cm (mean 1.3 6 0.8 cm). The mean light fluence rate at 0.5 cm from the CDF was 126 6 48 mW/cm 2 (N 5 22) when the total power from the fiber was 375 mW (150 mW/cm). This study showed significant inter-and intraprostatic differences in the optical properties, suggesting that a real-time dosimetry measurement and feedback system for monitoring light fluences during treatment should be advocated for future PDT studies. However, no significant changes were observed before, during and after PDT within a single treatment site.