Preclinical Study of the Novel Vascular Occluding Agent, WST11, for Photodynamic Therapy of the Canine Prostate
| Autor: | Hervé Ficheux, Maurice Anidjar, Eleonora Scarlata, Simone Chevalier, Lucie Hamel, Nicolas Borenstein, Avigdor Scherz, Mostafa M. Elhilali, Laurence Fiette |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Canine prostate Pathology medicine.medical_specialty medicine.diagnostic_test business.industry Urology medicine.medical_treatment Drug Evaluation Preclinical Prostate Cmax Photodynamic therapy Dogs Blood pressure medicine.anatomical_structure Photochemotherapy Pharmacokinetics Drug control medicine Animals Blood test business Bacteriochlorophylls |
| Zdroj: | Journal of Urology. 186:302-309 |
| ISSN: | 1527-3792 0022-5347 |
| Popis: | Vascular targeted photodynamic therapy with WST09 shows promise for recurrent prostate cancer after radiation but hydrophobicity in aqueous solutions limited application. We tested the safety and efficacy of WST11, a novel water soluble vascular occluding agent, for vascular targeted photodynamic therapy of the dog prostate and compared it to WST09 vascular targeted photodynamic therapy.Optical fibers were inserted in the prostate and connected to diode lasers. WST11 (Steba Biotech, Cedex, France) at varying doses, including a drug control with no light in 34 dogs, and WST09 (Steba Biotech) (2 mg/kg) in 3 dogs were infused during 10 minutes. Illumination was initiated at 5 or 10 minutes, and lasted up to 33.2 minutes based on laser fluence and delivered energy. Blood was collected for analysis and pharmacokinetics. The end point was at 1 week.No vascular targeted photodynamic therapy associated change was observed in blood pressure or blood test values. Circulating WST11 increased with drug infusion and decreased rapidly during 1 hour to reach undetectable levels by 24 hours. All except 1 dog with bowel intussusception did well after vascular targeted photodynamic therapy with only mild urinary symptoms that resolved within 24 to 48 hours. Lung and liver were normal. Hemorrhage was present in all prostates except controls. This translated into necrosis at a WST11 threshold and within a window of doses at fixed illumination. Necrosis was associated with loss of the vessel endothelial layer. Fluence highly impacted necrosis. WST11 vascular targeted photodynamic therapy was advantageously comparable to WST09 vascular targeted photodynamic therapy, and optimally ablated about 5.0 cm(3) of tissue per lobe and about 10 cm(3) of the whole prostate.The safety and efficacy of WST11 vascular targeted photodynamic therapy in the dog prostate support clinical applications for prostate cancer and benign prostatic hyperplasia. |
| Databáze: | OpenAIRE |
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