Functional and histological damage in the mouse bladder after photodynamic therapy

Abstract

Summary Bladders of anaesthetised mice were illuminated with laser light of 630 nm at 24 h after intraperitoneal administration of the photosensitiser Photofrin 11 (10 mg kg-'). A range of light doses, at a power setting of 100 mW, was delivered intravesically by a fibre optic inserted into the centre of the bladder via the urethra. Functional bladder damage was assessed from increases in urination frequency and the presence of haematuria at I to 26 weeks after treatment. Whole bladder illumination with incident light doses exceeding 18.75 J cm-2 caused extensive oedema, haemorrhage and necrosis of the bladder wall and mice had to be sacrificed within 24 h. PDT with incident light doses of 3.75 to 15.0 J cm 2 caused haematuria and increased urination frequency during the first week in nearly all mice, but there was complete functional recovery by 6 to 10 weeks after doses of up to 7.5 J cm-2. Recovery was slower after higher doses and up to 50% of mice still had some increased urination frequency at 10 weeks after > 11.25 J cm-2, although haematuria was rare at this time. Histologically, early damage (one day after PDT) consisted of epithelial sloughing, submucosal oedema, fibrin imbibition, vascular extasia and, rarely, thrombosis. Doses exceeding 7.5 J cm-2 were often associated with foci of necrosis. In some instances, necrosis was complicated by bacterial infection, resulting in an acute transmural inflammation with a tendency to suppuration. After doses of up to 11.25 J cm-2 there was a gradual recovery and only a mild degree of fibrosis of the bladder wall (with some increase in vascularity) remained at 6 months.

Photodynamic therapy of rat bladder and urethra: evaluation of urinary and reproductive function after inducing protoporphyrin IX with 5‐aminolaevulinic acid

“…Because the UFI derived from daily urinary spots for rats of moderate size (160–200 g) over the 2 weeks before PDT was so consistent, this method was adopted for the present study. Despite the differences in the animal model, animal size and experimental design from that of Stewart et al , the increased voiding irritation seen in the first 2 weeks after PDT in the present study was comparable to that reported in theirs, which used Photofrin II (10 mg/kg) in the H3C mouse bladder [29,30]. They concluded that the UFI and the time interval to return to normal voiding was linearly related to the dose of light.…”

“…Stewart et al [29] used a rolling‐paper device to determine the UFI, but the present method for assessing urinary frequency was simpler. However, the accuracy of this method in evaluating the real voiding frequency remains to be clarified.…”

Optimization of differential photodynamic effectiveness between normal and tumor urothelial cells using 5-aminolevulinic acid-induced protoporphyrin IX as sensitizer

“…1,2 Epithelial selectivity is an important pharmacological property since it targets cancer therapy to cells of interest, avoiding the direct damage of photodynamic therapy (PDT) in adjacent stromal cells, 3,4 as has been found with other photosensitizers. 5,6 In bladder tumors, 5-ALA has also proven useful for diagnostic purposes since a high sensitivity of tumor detection and flat tumor precursors were found on fluorescence endoscopy by applying a filtered lamp system and detecting red fluorescent lesions, caused by intracellular PPIX accumulation. [7][8][9] These findings are supported by genetic analyses of the urothelial lesions detected by PPIX fluorescence since they showed tumor-like genetic changes even in lesions such as hyperplasias, normally diagnosed as benign.…”

On the Development of a Light Dosimetry Planning Tool for Photodynamic Therapy in Arbitrary Shaped Cavities: Initial Results

“…Insufficient fluence rate will negatively affect the phototoxic reactions within the cell (1)(2)(3)6,7). High fluence rates may cause adverse reactions such as extensive edema, severe mucositis, increased pain perception, unintended necrosis and hyperthermia (1)(2)(3)5,(8)(9)(10). A low fluence rate requires an extended illumination time to achieve an effective light dose (1)(2)(3)(4)(5)(6)(7)(8)(9)(10).…”

“…High fluence rates may cause adverse reactions such as extensive edema, severe mucositis, increased pain perception, unintended necrosis and hyperthermia (1)(2)(3)5,(8)(9)(10). A low fluence rate requires an extended illumination time to achieve an effective light dose (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). It is widely accepted that an empirically determined light dose of 20 JÁcm À2 at a fluence rate of 100 mWÁcm À2 (k = 652nm) to the target area results in an optimal response to m-THPC (dose 0.15 mg kg À1 body weight)-mediated PDT of the head and neck area (11)(12)(13)(14)(15)(16)(17)(18).…”