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W M Star

Publications and source records attributed to W M Star.

At least 19 recordsLinked to original sources
PubMed1997

Photobleaching during and re-appearance after photodynamic therapy of topical ALA-induced fluorescence in UVB-treated mouse skin.

Photodynamic therapy (PDT) using protoporphyrin IX (PpIX) induced by topically applied 5-aminolevulinic acid (ALA) seems a promising alternative for the treatment of superficial non-melanoma skin cancer and actinic keratosis. In this study, the kinetics of new PpIX fluorescence arising after a PDT treatment that had photobleached the original fluorescence were determined. Our purpose was to examine the feasibility of multiple irradiations, following a single topical ALA application, to increase PDT efficacy. In addition, photobleaching during PDT and the fluorescence spectra during and after PDT were studied. As a model we used hairless mice with and without UVB-induced skin lesions. ALA was applied to the skin for 4 hr. An illumination was delivered either immediately after application or 6 hr after the end of the application (at interval of maximum fluorescence). During PDT, the fluorescence of normal skin decreased at a faster rate than the fluorescence of the skin lesions. In the fluorescence study after PDT, the areas treated immediately post-application showed a fluorescence increase over time similar to that in non-treated areas on the same mice. A remarkable result was that the fluorescence of areas treated at maximum fluorescence increased, whereas the fluorescence of non-treated areas did not increase over time. With both treatment intervals the new fluorescence showed a characteristic PpIX spectrum. Our results demonstrate that a second illumination, when new PpIX fluorescence has been formed, may increase PDT efficacy after topical ALA application. This finding has been demonstrated previously for systemic ALA administration.

Administration, Topical↗
PubMed1997

Bladder PDT with intravesical clear and light scattering media: effect of an eccentric isotropic light source on the light distribution.

BACKGROUND AND OBJECTIVE: Whole bladder wall photodynamic therapy (PDT) is sometimes performed with a light scattering medium in the bladder, as it is assumed that this will promote a more uniform illumination of the bladder wall. The influence of eccentric placement of an isotropic light emitting diffuser on the homogeneity of the light distribution at the bladder wall is assessed. STUDY DESIGN/MATERIALS AND METHODS: Whole bladder wall irradiations were performed at approximately 630 nm, and fluence rates were measured with and without controlled amounts of Intralipid in an ex vivo pig bladder and in vitro in a bladder phantom. Experimental values were compared to Monte Carlo simulations using in vitro bladder optical properties. RESULTS: An eccentric diffuser in a clear intravesical medium produces a better uniform illumination than in a light scattering intravesical medium. Also, intravesical light absorption, e.g., by urine, would lead to a substantial loss of the energy delivered in case of light scattering cavity contents. CONCLUSION: The use of a clear intravesical medium guarantees the highest and most uniform fluence rate at the bladder wall during optical irradiation with an isotropic light source in clinical PDT of nonspherical bladders, whereas an intravesical light scattering medium reduces both the magnitude and the uniformity of the fluence rate.

Animals↗
PubMed1997

Photofrin-mediated photodynamic therapy of chemically-induced premalignant lesions and squamous cell carcinoma of the palatal mucosa in rats.

Photodynamic therapy (PDT), an experimental cancer therapy, was studied in an animal model of chemically-induced epithelial dysplasia and squamous cell carcinoma. PDT was performed 24 hours after i.v. injection of 2.5 mg/kg bw Photofrin, and using 100 J/cm2 incident light at two activation wavelengths (514.5 nm or 625 nm). Two days after PDT, the majority of rats macroscopically showed a marked erythema of the entire palatal region. Microscopically all the rats showed oedema, haemorrhage, and necrosis of the epithelium of the intermolar area. The long-term results were not so favourable. No evidence of disease was found in 6 out of 20 rats in the 514.5 nm group and in 2 out of 20 rats in the 625 nm treated group. Epithelial dysplasia was found in 14 out of 20 rats in the 514.5 nm group, and in 18 out of 20 rats of the 625 nm treated group. Squamous cell carcinomas were found in 4 out of 20 rats treated with 514.5 nm and in 7 out of 20 rats in the 625 nm treated groups. Comparing both treatment wavelengths, better results were obtained in the 514.5 nm groups as this wavelength gave less normal tissue damage. Based on the results of this study the application of PDT for the treatment of field cancerization and squamous cell carcinoma of the oral cavity, is discussed.

4-Nitroquinoline-1-oxide↗
PubMed1997

In vivo photo-detection of chemically induced premalignant lesions and squamous cell carcinoma of the rat palatal mucosa.

Photo-detection using in vivo fluorescence was studied for different stages of chemically induced premalignant lesions and squamous cell carcinoma (SCC) of the Wistar rat palatal mucosa. It was found that the epithelial dysplasia (numerically expressed in the epithelial atypia index (EAI) of the rat palate, induced by repeated application of the carcinogen 4-nitroquinoline 1-oxide (4NQO), showed an increase approximately proportional to the duration of the application period. Photo-detection of the lesions using Photofrin-induced fluorescence was studied with dual-wavelength excitation and the subtraction of images, in an attempt to reduce the autofluorescence. The Photofrin dose was 2.5 mg kg-1. This was based on a dose-response study for normal tissue damage by photodynamic therapy (PDT) in this animal model, because the underlying rationale was to study photo-detection as a method of locating additional (early) malignancies in patients treated by PDT. Fluorescence intensities 24 and 48 h after injection of Photofrin were shown to increase with the duration of 4NQO application and with increasing EAI. For an EAI greater than 15, there was a statistically significant difference (p < 0.01) between the fluorescence signals obtained with and without the injection of Photofrin. Fluorescence signals of these lesions without the use of Photofrin (autofluorescence) also showed an increase with increasing stages of epithelial dysplasia of the rat palate. However, the fluorescence signals obtained with Photofrin were always higher than those of the autofluorescence. From this study, we conclude that photo-detection with Photofrin has potential in distinguishing chemically induced premalignant lesions and squamous cell carcinomas from the normal rat palatal mucosa. Photofrin (2.5 mg per kg of body weight) certainly adds to the sensitivity of photo-detection, but autofluorescence alone also has promising features for detecting premalignant and malignant lesions of the oral mucosa.

4-Nitroquinoline-1-oxide↗
PubMed1997

Light dosimetry in vivo.

This paper starts with definitions of radiance, fluence (rate) and other quantities that are important with regard to in vivo light dosimetry. The light distribution in mammalian tissues can be estimated from model calculations using measured optical properties or from direct measurements of fluence rate using a suitable detector. A historical introduction is therefore followed by a brief discussion of tissue optical properties and of calculations using diffusion theory, the P3-approximation or Monte Carlo simulations. In particular the form of the scattering function is considered in relation to the fluence rate close to the tissue boundary, where light is incident. Non-invasive measurements of optical properties yield the absorption coefficient mu a and mu s(1 - g), where mu s is the scattering coefficient and g is the mean cosine of the scattering angle. An important question is whether this combination is sufficient, or whether g itself must be known. It appears that for strongly forward scattering, as in mammalian tissues, rather detailed knowledge of the scattering function is needed to reliably calculate the fluence rate close to the surface. Deeper in the tissue mu s (1 - g) is sufficient. The construction, calibration and use of fibre-optic probes for measurements of fluence rate in tissues or optical phantoms is discussed. At present, minimally invasive absolute fluence (rate) measurements seem to be possible with an accuracy of 10-20%. Examples are given of in vivo measurements in animal experiments and in humans during clinical treatments. Measurements in mammalian tissues, plant leaves and marine sediments are compared and similarities and differences pointed out. Most in vivo light fluence rate measurements have been concerned with photodynamic therapy (PDT): Optical properties of the same normal tissue may differ between patients. Tumours of the same histological type may even show different optical properties in a single patient. Treatment-induced changes of optical properties may also occur. Scattered light appears to contribute substantially to the light dose. All these phenomena emphasize the importance of in situ light measurements. Another important dosimetric parameter in PDT is the concentration and distribution of the photosensitizer. Apart from in vivo fluorescence monitoring, the photosensitizer part of in vivo PDT dosimetry is still in its infancy.

Animals↗
PubMed1997

Improvements in the design of linear diffusers for photodynamic therapy.

The angular radiance distribution of several linear diffusers used for photodynamic therapy (PDT) was measured. The forward scattering found previously was not observed for these designs. The improved isotropy leads to a better agreement between intended treatment site and actual maximum of the fluence rate profile when the linear diffuser is used in a hollow, cylindrical organ.

Diffusion↗
PubMed1997

Distribution of aluminum phthalocyanine disulfonate in an oral squamous cell carcinoma model. In vivo fluorescence imaging compared with ex vivo analytical methods.

Photosensitizer-induced fluorescence is studied as a technique for the detection of cancer. Therefore we investigated the ability of a photosensitizer, aluminum phthalocyanine disulfonate (AIPcS2), to localize in tumor tissue. In vivo endoscopic fluorescence imaging, fluorescence microscopy, conventional spectrofluorometry and high performance liquid chromatograpy combined with diode laser-induced fluorescence (HPLC-Dio-LIF) were used. Squamous cell carcinomas were induced with 4-nitro-quinoline-1-oxide (4NQO) in the mucosa of the palate of the rat. In vivo fluorescence images, taken after injection of 1.5 mumol/kg AIPcS2 intravenously, showed that 4NQO-treated palates had higher fluorescence signals than normal palates. Areas displaying locally high amounts of AIPcS2 fluorescence (hot spots) were present only in 4NQO-treated rats 2-8 h but had disappeared 24 h after injection. However, HPLC-Dio-LIF showed that the relative AIPcS2 content was highest at 24/48 h in biopsies taken in the areas of the hot spots. Fluorescence microscopy revealed that AIPcS2 was present only between 2 and 8 h in the epithelial layer, while in biopsies the connective tissue contained large quantities of AIPcS2 at 24/48 h. In vivo fluorescence imaging appears to show mainly fluorescence from the epithelial layer and the ex vivo analytical techniques mainly show the connective tissue fluorescence. Care should be taken when interpreting data using one technique only.

Animals↗
PubMed1996

Evidence for an important role of neutrophils in the efficacy of photodynamic therapy in vivo.

To investigate the role of neutrophils in the efficacy of photodynamic therapy (PDT) in rhabdomyosarcoma-bearing rats, the number of these circulating phagocytes was decreased or increased before interstitial PDT by use of rabbit anti-rat neutrophil serum or granulocyte colony-stimulating factor, respectively. After administration of the antiserum, the number of circulating neutrophils decreased by 99.9%. However, the number of monocytes, lymphocytes, and platelets decreased as well (by 100%, 80%, and 25%, respectively). Under these conditions, PDT did not retard tumor growth at all. However, after cessation of the antiserum treatment 5 days after PDT, a striking decrease in the growth rate occurred subsequent to an increase above the normal range of the number of circulating neutrophils. Administration of the granulocyte colony-stimulating factor led to a specific 4-fold increase in the number of circulating neutrophils. In these rats, the tumor growth at day 2 after PDT was retarded as compared with PDT-treated rats that received saline only. Statistical evaluation of both experimental conditions showed that the efficacy of PDT, expressed as the percentage of change in tumor volume at day 2 after treatment, was dependent on the number of circulating neutrophils present at the day of PDT (P = 0.001; r2 = 0.482). Apparently, neutrophils are indispensable for successful PDT in vivo.

Animals↗
PubMed1996

Photodynamic therapy: a promising new modality for the treatment of cancer.

The first reports on photodynamic therapy (PDT) date back to the 1970s. Since then, several thousands of patients, both with early stage and advanced stage solid tumours, have been treated with PDT and many claims have been made regarding its efficacy. Nevertheless, the therapy has not yet found general acceptance by oncologists. Therefore it seems legitimate to ask whether PDT can still be described as "a promising new therapy in the treatment of cancer". Clinically, PDT has been mainly used for bladder cancer, lung cancer and in malignant diseases of the skin and upper aerodigestive tract. The sensitizer used in the photodynamic treatment of most patients is Photofrin, (Photofrin, the commercial name of dihematoporphyrin ether/ester, containing > 80% of the active porphyrin dimers/oligomers (A.M.R. Fisher, A.L. Murphee and C.J. Gomer, Clinical and preclinical photodynamictherapy, Review Series Article, Lasers Surg. Med., 17 (1995) 2-31). It is a complex mixture of porphyrins derived from hematoporphyrin. Although this sensitizer is effective, it is not the most suitable photosensitizer for PDT. Prolonged skin photosensitivity and the relatively low absorbance at 630 nm, a wavelength where tissue penetration of light is not optimal, have been frequently cited as negative aspects hindering general acceptance. A multitude of new sensitizers is currently under evaluation. Most of these "second generation photosensitizers" are chemically pure, absorb light at around 650 nm or greater and induce no or less general skin photosensitivity. Another novel approach is the photosensitization of neoplasms by the induction of endogenous photosensitizers through the application of 5-aminolevulinic acid (ALA). This article addresses the use of PDT in the disciplines mentioned above and attempts to indicate developments of PDT which could be necessary for this therapy to gain a wider acceptance in the various fields.

Digestive System Neoplasms↗
PubMed1996

In vivo fluorescence kinetics and localisation of aluminum phthalocyanine disulphonate in an autologous tumour model.

Sulphonated phthalocyanines are studied as photosensitizers for photodynamic therapy of cancer. Their strong fluorescence and tumour-localising properties make them also potentially useful for detection of cancer by fluorescence. For this purpose, we have studied the fluorescence kinetics and localisation of aluminum phthalocyanine disulphonate (AlPcS2) in 4-nitroquinoline 1-oxide (4NQO)-induced dysplasia and invasive cancer of the oral mucosa of the hard palate in Wistar albino rats. Twenty-two rats were divided into six groups. Five groups were subjected to a 4NQO application period of 8, 12, 16, 20 or 26 weeks and one was a control group. The dysplasia varied from slight to severe and was correlated with the duration of the application period. All animals received a dose of 1 micromol/kg AlPcS2 i.v. Fluorescence images were recorded via a specially designed 'palatoscope' with excitation at 460 +/- 20 nm for autofluorescence, 610 +/- 15 nm for AlPcS2 fluorescence and detection of emission at 675 +/- 15 nm. After subtraction of the two images the specific AlPcS2 fluorescence remained. AlPcS2-mediated fluorescence increased significantly when the severity of dysplasia increased (P<0.04). Also the phenomenon of strong fluorescent spots on the fluorescence images was observed. This always occurred within the first 10 h after injection of AlPcS2. Histological analysis showed a local alteration to a mucosa in 67% of these spots, which was either invasive cancer (29%) or inflammation (38%). These results suggest two different mechanisms of AlPcS2 uptake in tissue, one associated with the presence of generalised dysplasia and another associated with local changes of the epithelial/connective tissue, which is not necessarily specific for tumours.

4-Nitroquinoline-1-oxide↗
PubMed1996

Kinetics and localisation of PpIX fluorescence after topical and systemic ALA application, observed in skin and skin tumours of UVB-treated mice.

In this study the kinetics and localisation of protoporphyrin IX (PpIX) fluorescence in skin and skin tumours were examined after topically (20% for 4h) or systemically (200 mg/kg,i.p.) administered 5-aminolaevulinic acid (ALA). As a model we used hairless mice with skin lesions (actinic keratoses and squamous cell carcinoma), which were induced by daily UVB irradiation. The epidermis of the skin surrounding the tumours (T) was altered (AS); owing to the UVB irradiation, the epidermis was thicker and less elastic. Therefore, non-UVB-irradiated mice were used to assess fluorescence of normal skin (NS). Light from a halogen lamp was used to excite at 500 +/- 20 nm and fluorescence was detected through a filter that passes light of 670 +/- 50 nm. Maximal fluorescence following i.p. ALA was observed 2 h post injection (p.i.) and was three times less than after topically applied ALA. Furthermore, after i.p. ALA a lower T selectively (T/NS) could be obtained than after topically applied ALA. Maximal fluorescence following topically applied ALA was achieved 6 h after the end of the 4 h application time. At that interval fluorescence of T was twice as high as directly after the application period. Furthermore, T selectivity (T/NS) after topical ALA at the interval of maximal fluorescence was higher than at the interval directly after application. With fluorescence cryomicroscopy localisation of fluorescence in the skin at the interval of maximal fluorescence was determined after both administration routes. For both cases fluorescence was mainly located in T, epidermis and hair follicles. Fluorescence in subcutis could only be observed at 2 h post i.p. ALA and a 6 h post topical ALA. No fluorescence could be observed in muscle. We conclude that, in this model and with these ALA doses, a higher fluorescence intensity and selectivity (T/NS) was achieved after topically applied ALA than after systemically administered ALA. These results make topically applied ALA more favourable for ALA-PDT of superficial skin tumours in this model. In general these results imply that by optimising the time after ALA application the efficacy and selectivity of topical ALA-PDT for skin tumours may be improved.

Administration, Topical↗
PubMed1996

Integrating sphere effect in whole-bladder wall photodynamic therapy: III. Fluence multiplication, optical penetration and light distribution with an eccentric source for human bladder optical properties.

Whole-bladder-wall (WBW) photodynamic therapy (PDT) is performed using approximately 630 nm light emitted by an isotropic light source centered in the bladder cavity. The phenomenon of an increased fluence rate in this spherical geometry, due to light scattering, is denoted as the integrating sphere effect. The fluence rate and the optical penetration depth depend on a single tissue optical parameter, namely the reduced albedo. The optical properties of (diseased) human bladder tissue, i.e. absorption coefficient, scattering coefficient, anisotropy factor and refractive index, were determined in vitro in the wavelength range of 450-880 nm. The integrating sphere effect and optical penetration depth were calculated with diffusion theory and compared to Monte Carlo (MC) computer simulations using approximately 630 nm optical properties. With increasing albedo, the integrating sphere effect calculated with diffusion approximation is increasingly larger than that found with MC simulations. Calculated and simulated optical penetration depths are in reasonable agreement. The smaller the integrating sphere effect for a given tissue absorption, the larger the optical penetration depth into the bladder wall, as the effective attenuation coefficient decreases. Optical penetration depths up to approximately 7.5 mm (definition dependent) can be responsible for unintended tissue damage beyond the bladder tissue. MC simulations were also performed with an eccentric light source and the uniformity of the light distribution at the bladder wall was assessed. The simulations show that even for a small eccentricity, the extremes in deviation from the mean fluence rate are large. All these results indicate that WBW PDT should be performed with some kind of in situ light dosimetry.

Cystitis↗
PubMed1996

Light distribution by linear diffusing sources for photodynamic therapy.

The distribution of the light emitted by linear light diffusers commonly employed in photodynamic therapy (PDT) has been investigated. A device is presented which measures the angular distribution of the exiting light at each point of the diffuser. With these data the fluence rate in air or in a cavity at some distance from the diffuser can be predicted. The results show that the light is scattered from the diffuser predominantly in the forward direction. Experiments and calculations show that the fluence rate in air and in a cavity of scattering tissue at some distance from the diffuser has a maximum near the tip of the diffuser, instead of near the middle. However, the fluence rate resulting from an interstitial diffuser in a purely scattering tissue phantom shows a maximum in the bisecting plane of the diffuser as would be predicted when the diffuser emitted light isotropically. The scattering nature of the tissue is expected to cancel the anisotropy of the diffuser.

Animals↗
PubMed1996

Calibration of isotropic light dosimetry probes based on scattering bulbs in clear media.

Miniature light detectors with isotropic response (isotropic light probes) permit quantitative measurement of light energy fluence rates in turbid media such as biological tissues. These isotropic probes are, for example, applied in photodynamic therapy to correlate light fluence in tissue with (tumour) tissue response, in vitro and in vivo. After description of its construction, two methods of calibration of an isotropic probe in air are discussed, in collimated and in diffuse light. The probe was first calibrated in air in collimated light, after which its response to diffuse light was checked in a flat and in a spherical geometry. Subsequently, the probe's response to collimated light in clear media, for example, water or glycerine which have refractive indices larger than that of air, has been established experimentally. The diffusion approximation to the transport equation in a simple spherical geometry has been used to calculate the probe's response as a function of the refractive index of clear media. The extent of agreement between theory and experiment indicates that the physical mechanisms are understood and indirectly validates the theoretical models.

Humans↗
PubMed1996

Photodynamic therapy of oral cancer. A review of basic mechanisms and clinical applications.

Photodynamic therapy (PDT) is an experimental cancer treatment modality. PDT is based on the accumulation of a photosensitive dye in premalignant and malignant lesions. A certain period of time after the dye has been administered, tumor tissue may contain more of the sensitizer then the surrounding normal tissues. When tissue containing the sensitizer is exposed to light of a proper wavelength and dose, a photochemical reaction between sensitizer and light will occur. The activated photosensitizer reacts with available oxygen which subsequently damages cells and eventually may cause necrosis of the tumor. Photosensitizers can also be used for fluorescence detection. If a tumor contains more of the photosensitizer than the surrounding normal tissue, its fluorescence can potentially be utilized to detect tumors. Analogous to PDT, this can therefore be referred to as photodynamic detection (PDD). This paper reviews the basic mechanisms and clinical applications of PDT and PDD. Emphasis is placed on PDD and PDT with the photosensitizer Photofrin for detection and treatment of premalignant epithelial lesions and squamous cell carcinomas of the oral mucosa.

Carcinoma, Squamous Cell↗
PubMed1995

The relationship between integrating sphere and diffusion theory calculations of fluence rate at the wall of a spherical cavity.

The radiant energy fluence rate has been calculated at the wall of a spherical cavity, filled with a non-scattering and non-absorbing material, in a scattering and absorbing infinite medium, illuminated by an isotropic point light source at the centre. Two methods have been used: first, diffusion theory for a spherical geometry; second, integrating sphere theory using reflection factors obtained from diffusion theory for a plane semi-infinite medium illuminated by either a broad collimated perpendicularly incident beam or a broad diffuse incident beam. The two methods give identical results if the condition for the validity of the diffusion approximation is satisfied, that is mu(a) << mu(s) (mu(a) = optical absorption coefficient, mu(s) = scattering coefficient) and if also mu(eff)r1 >> 1, where r1 is the radius of the cavity and mu(eff) is the effective optical attenuation coefficient of the medium. Under the same conditions, the two methods also give identical results when the refractive index of the medium is larger than the refractive index of the material in the cavity. A numerical estimate using optical properties of human bladder indicates that the conditions for validity of the integrating sphere approach are nearly satisfied in whole-bladder photodynamic therapy.

Diffusion↗
PubMed1995

Ex vivo light dosimetry and Monte Carlo simulations for endobronchial photodynamic therapy.

The light distribution during photodynamic therapy of the bronchial tree has been estimated by measuring the fluence rate in ex vivo experiments on dissected pig bronchi. The trachea was illuminated (630 nm) with a cylindrical diffuser and the fluence rate was measured with a fibre optic isotropic probe. The experiment with the diffuser on the central axis was also simulated with Monte Carlo techniques using the optical properties that were determined with a double-integrating-sphere set-up. The results from ex vivo experiments and the Monte Carlo simulations were found to agree within the error of measurement (15%), indicating that the Monte Carlo technique can be used to estimate the light distribution for varying geometries and optical properties. The results showed that the light fluence rate in the mucosa of the tracheal tract may increase by a factor of six compared to the fluence rate in air (in the absence of tissue). This is due to the scattering properties of the tissue and the multiple reflections within the cavity. Further ex vivo experiments showed that the positioning of the diffuser is critical for the fluence rate in the lesion to be treated. When the position of the diffuser was changed from the central axis to near the lesion, the fluence rate in the mucosa increased significantly by several orders of magnitude as compared to the initial (central) illumination. The inter- and intraspecimen variations in this increase were large (+/- 35%) because of variations in optical and geometrical properties and light source positioning, respectively. These variations might cause under- or overdosage resulting in either insufficient tumour necrosis or excessive normal tissue damage.

Animals↗