Photobleaching of protoporphyrin IX in cells incubated with 5-aminolevulinic acid

Moan, Johan Emelian; Streckyte, Giedre; Bagdonas, Saulius; Bech, Øystein; Berg, Kristian

doi:10.1002/(sici)1097-0215(19970106)70:1<90::aid-ijc14>3.0.co;2-h

Cited by 120 publications

(87 citation statements)

References 26 publications

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“…In contrast to recent findings of Robinson et al [19] in hairless mice and of Georgakoudi et al [29] in vitro, a double exponential decay fitted our photobleaching curves better than fitting according to a second order process. Also, Moan et al [30] described the PpIX decay during PDT in vitro by a sum of two exponential terms, which is in agreement with our study. These authors ascribed this characteristic to the relocation of the photosensitizer during PDT or its chemical modification that contributes to the photobleaching process.…”

Section: Photobleaching Monitoring and Ros Reporter Systemsupporting

confidence: 92%

Hexyl‐aminolevulinate‐mediated photodynamic therapy: How to spare normal urothelium. An in vitro approach

et al. 2006

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Background and Objectives: Photodynamic therapy (PDT) of superficial bladder cancer may cause damages to the normal surrounding bladder wall. Prevention of these is important for bladder healing. We studied the influence of photosensitizer concentration, irradiation parameters, and production of reactive oxygen species (ROS) on the photodynamically induced damage in the porcine urothelium in vitro. The aim was to determine the threshold conditions for the cell survival. Methods: Living porcine bladder mucosae were incubated with solution of hexylester of 5-aminolevulinic acid (HAL). The mucosae were irradiated with increasing doses and cell alterations were evaluated by scanning electron microscopy and by Sytox green fluorescence. The urothelial survival score was correlated with Protoporphyrin IX (PpIX) photobleaching and intracellular fluorescence of Rhodamine 123 reflecting the ROS production. Results: The mortality ratio was dependent on PpIX concentration. After 3 hours of incubation, the threshold radiant exposures for blue light were 0.15 and 0.75 J/cm 2 (irradiance 30 and 75 mW/cm 2 , respectively) and for white light 0.55 J/cm 2 (irradiance 30 mW/cm 2 ). Photobleaching rate increased with decreasing irradiance. Interestingly, the DHR123/R123 reporter system correlated well with the threshold exposures under all conditions used. Conclusions: We have determined radiant exposures sparing half of normal urothelial cells. We propose that the use of low irradiance combined with systems reporting the ROS production in the irradiated tissue could improve the in vivo dosimetry and optimize the PDT. Lasers Surg.

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Section: Photobleaching Monitoring and Ros Reporter Systemsupporting

confidence: 92%

Hexyl‐aminolevulinate‐mediated photodynamic therapy: How to spare normal urothelium. An in vitro approach

et al. 2006

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“…This is indicative of a "fast", most pertinent to an urologist, and a "slow" component in the photobleaching of PpIX. Publications 15,16 by others groups confirm this observation. Focusing on the fast component, of photobleaching at 430 and 525 nm respectively, it can be inferred from the fitting parameters in Table 1 .…”

Section: Photobleachingsupporting

confidence: 59%

Method for improving photodynamic diagnosis and surgery of bladder tumours using cystoscopes

Lindvold

Hermann

2015

SPIE Proceedings

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We present a new concept on how to remove unwanted green fluorescence from urine during Photodynamic Diagnostics of tumours in the bladder using cystoscopy. A high power LED based light source (525 nm) has been made in our laboratory. This light source is tailored to match most commercially available rigid cystoscopes. A suitable spectral filter and adapter, for the eyepiece of the cystoscope, has been selected which allows the urologist to observe both red fluorescence from tumours and autofluorescence from healthy tissue at the same time.

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“…Considering the photobleaching of porphyrins during irradiation (Rotomski et al, 1996;Bezdetnaya et al, 1996;Moan et al, 1997), a threshold concentration of PpIX necessary for tissue destruction, and the high selectivity of h-ALA-induced PpIX, a small PpIX amount in healthy areas of the bladder, observed in this study will probably not induce any damage in these regions. However, the twofold increase of PpIX fluorescence after 6 h in neoplastic tissues by using h-ALA may further enhance the PDT effect as compared to the use of ALA.…”

Section: Discussionmentioning

confidence: 79%

Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study

et al. 1999

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Fluorescence photodetection (PD) and photodynamic therapy (PDT) are techniques currently under clinical assessment for both visualization and local destruction of malignant tumours and premalignant lesions. One drawback of these methods found with some photosensitizers is a more or less long-term cutaneous photosensitivity (Wagnières et al, 1998;Dougherty et al, 1990). A more recent strategy for administering photosensitizers involves the application of 5-aminolaevulinic acid (ALA) in order to stimulate the formation of protoporphyrin IX (PpIX) in situ. The exogenous ALA bypasses the negative feedback control from haem to ALA synthase that catalyses the condensation of glycine and succinyl-coenzyme A (CoA). Given in excess, exogenous ALA thus can result in a temporary accumulation of PpIX, in particular, in cells with higher metabolic turnover. Since PPIX has fairly good photosensitizing properties (Cox et al, 1982;Kennedy et al, 1990) proposed ALA as a possible photodynamic agent. Following this pioneering work, this treatment modality has been widely studied for various cancers (Kennedy et al, 1992;Peng et al, 1992;Svanberg et al, 1994).As well as for the PDT of malignant or premalignant lesions, ALA-induced PpIX is now being used for the detection of such lesions. This technique has been shown to work, among other applications, in urology, where easy instillation in the bladder, combined with the fact that this organ is readily accessible endoscopically, makes it an ideal object. Alongside classical techniques such as cytology or white light examination, fluorescence PD by ALA-induced PpIX provides some advantages (Leveckis et al, 1994;Kriegmair et al, 1996;Jichlinski et al, 1997). This inspection modality allows an exact mapping which pinpoints, with a high level of sensitivity and specificity, the locations of carcinoma in situ (CIS) as well as early stages of cancer-like dysplasias, which are normally difficult to recognize under white light examination.However, when using topically instilled ALA for the PDT of CIS and precancerous lesions, this modality appears to be limited by the amount of ALA that enter the target cells or by the tissue penetration and the distribution of the resulting PpIX in the targeted tissue. Almost all of these possible disadvantages accompanying the use of ALA can be ascribed to the physical-chemical properties of the molecule itself. Applied under physiological conditions, ALA is a zwitterion (Novo et al, 1996). Because the lipid bilayer of biological membranes is relatively impermeable to charged molecules, the cellular uptake of ALA is shallow. Consequently, in order to increase the transport across cellular membranes, fairly high drug doses and increased administration times have to be used. This deficiency results in a low penetration depth (Warloe et al, 1992;Loh et al, 1993;Peng et al, 1995) and an ALA-induced PpIX distribution, which is not optimized for the PDT of the deep layers of nodular lesions in the urothelium (Iinuma et al, 1995;Chang et al, 1996) after topical A...

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Photobleaching of protoporphyrin IX in cells incubated with 5-aminolevulinic acid

Cited by 120 publications

References 26 publications

Hexyl‐aminolevulinate‐mediated photodynamic therapy: How to spare normal urothelium. An in vitro approach

Hexyl‐aminolevulinate‐mediated photodynamic therapy: How to spare normal urothelium. An in vitro approach

Method for improving photodynamic diagnosis and surgery of bladder tumours using cystoscopes

Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study

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