PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.
This paper reviews the main approaches that have been made worldwide over the past five years (1989 - 1993) in the effort to discover new and more effective sensitizers for tumor phototherapy. Advances in our understanding of haematoporphyrin derivative and its commercial variants are dealt with briefly. New compounds in the porphyrin, chlorin, bacteriochlorin and phthalocyanine series are discussed, and the relationship between spectroscopic and other physical properties and the photoactivity of the drug are explored. The prospects for future developments are considered briefly.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Benzoporohyrin derivative monoacid ring A (BPD) is a lipophilic photosensitizer with a maximum absorption peak at 690 nm. When liposomally formulated, it distributes in human plasma almost exclusively to the lipoprotein fraction. In experimental animals and humans, it demonstrates good selectivity for tumors as well as other hyperproliferative tissues or cells. In experimental animal tumour models we have found maximum selectivity between tumour and normal surrounding tissue to occur within the first hour following intravenous administration, providing an opportunity for very early PDT following injection. Early clinical trial results from treatment of patients with cutaneous cancerous lesions have shown encouraging efficacy at levels of drug between 0.35 and 0.5 mg/kg. In addition, studies on patients with psoriasis indicate that BPD and light may be used to clear psoriatic plaques.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Aluminum phthalocyanine (AlPc) is a second-generation photosensitizer under study for photodynamic therapy (PDT) of cancer. Its mechanism of action is not known. Fluoride appears to be a powerful probe for the mechanistic study of AlPc derivatives. F- forms a complex with the Al ligand, resulting in drastically reduced AlPc-induced phototoxicity. This is due to a modified binding of AlPc with certain target proteins, resulting in inhibition of electron transfer reactions (type I) but not singlet oxygen reactions (type II). In Chinese hamster ovary (CHO) cell membranes, Na+/K+-ATPase activity is selectively protected by F- from photosensitized inhibition by AlPc, suggesting that this enzyme may be a critical target for AlPc-PDT. Another cellular response, not interfered with by F-, is a transient increase of cytoplasmic free Ca2+ after AlPc-PDT. This increase was shown to trigger the induction of a recovery process.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Zinc(II)-phthalocyanine (Zn-Pc) was chosen for development as a second-generation photosensitizer for photodynamic therapy (PDT) of tumors and for benign conditions because of its advantageous chemical and photophysical properties. Zn-Pc displayed good selectivity for malignant tissue in pharmacokinetic studies with Meth-A-sarcoma-bearing BALB/c mice when injected in a dose of 0.125 mg/kg, delivered by CGP 55 847. Intravenous doses of Zn- Pc ranging from 0.032 to 0.375 mg/kg caused tumor necrosis and, subsequently, cure of Meth-A-sarcoma-bearing mice when phototreatment was performed 48 hours after injection of CGP 55 847. Intravenous injection of Zn-Pc into hairless mice in doses ranging from 0.1 to 1.0 mg/kg caused dose- and time-dependent phototoxicity. We conclude that the promising pharmacological properties of liposomally delivered Zn-Pc, along with its advantageous chemical and photophysical properties, warrant the development of CGP 55 847 as a candidate drug for photodynamic therapy of tumors in humans.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Based on literature data obtained in various fields with respect to studies on the role of free radicals in biology and on the kinetics of triplet-doublet interactions, it is suggested that excited photosensitizers react in vivo with free radicals formed in malignant tissues during photodynamic therapy (PDT) and this interaction competes with sensitizer-radical + molecule and the singlet oxygen mediated effects. Experimental results by laser flash photolysis and electron spin resonance revealed that sensitizer applied in PDT react with stable free radicals presumably both by energy transfer and electron transfer.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Inherent in both plants and animals is the natural porphyrin, Protoporphyrin IX (Pp). Although Pp does not appear to have any intrinsic biological activity, it is a potent natural photosensitizer. When activated with ultraviolet or visible light, this photosensitizer can induce significant photodynamic effects on tissues, cells, subcellular elements, and macromolecules via the production of singlet oxygen. The biosynthesis of endogenous Pp is under strict enzymatic control. It is possible to bypass a rate controlling step and induce large, transient concentrations of Pp by the addition of exogenous 5-aminolevulinic acid (ALA). ALA may be administered systemically or topically. Much larger amounts of Pp are produced in certain types of tumor tissue than in adjacent normal tissue. Topically applied ALA can be used to treat a variety of skin lesions, including actinic keratosis, basal cell carcinomas and psoriasis.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The reactivity of the triplet state photosensitizer (hematoporphyrin) has been studied in model systems (homogeneous solutions). Preliminary experiments show that stable free radicals are consumed during interactions with triplet hematoporphyrin. These results combined with data in the literature enable the calculation of the relative importance of the interaction between the free radical and the triplet sensitizer as compared to the energy transfer from the triplet to ground state oxygen producing singlet oxygen. Our data are confirmed by direct measurements on the quantum yield of singlet oxygen in the absence and in the presence of stable free radicals.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
We developed a new water-soluble phthalocyanine, activated for coupling to antibodies by N- hydroxysulfosuccinimide. The efficiency of anti-CA125-phthalocyanine conjugates was compared to free phthalocyanine in a human ovarian carcinoma model in tissue culture. In both cases a dose dependent cell killing was observed after irradiation with a Titanium sapphire laser at 675 nm and 50 J/cm2, but incubation with antibody-coupled phthalocyanine resulted in 90% cell mortality with a 60-130-fold lower dye application.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Germanium-dihydroxy-phthalocyanine GePc(OH2) was synthesized and used as starting material for several new, axially disubstituted derivatives of the general formula GePc[OSi(R2)R']2. The preparation of the monosubstituted silanol side chains HOSi(R)2R' was performed either by Mitsunobu reaction starting from diphenylsilandiol Si(Ph)2(OH)2 followed by direct coupling of the side-chain with GePc(OH)2, or by synthesis from a dichlorosilyl derivative. The new compounds were fully characterized and the chemical and main photophysical properties determined. The absorption maxima of these compounds lie in the range of 675 nm. They were found to possess a high quantum efficiency of singlet-oxygen production and fluorescence. The compounds were incorporated into small, unilamellar liposomes following a technology developed by Ciba-Geigy. The dye-to-lipid ratio was 1:100. The liposomal suspensions were freeze-dried for storage. The new compounds were evaluated for their pharmacokinetic and phototherapeutic properties.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The pharmacokinetic and phototherapeutic properties of new phthalocyanines with Ge(IV) or Si(VI) as the central metal ion and cholesterol, cholestan or long-chain fatty acids residues as axial ligands to the central ion have been studied in tumor-bearing mice. The new photosensitizers were selectively taken up by and relatively quickly released from the tumors. Except for Si(IV)-Pc, which showed a comparably high selectivity for tumor versus peritumoral tissue, all Ge(IV)-Pc were less selective than liposomal Zn-Pc (CGP 55847). However, all the new compounds showed excellent phototherapeutic efficiency at very low drug and light doses in studies in Meth-A-sarcoma-bearing mice.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
A series of hydroxychlorins and another of (omega) -carboxyalkyloxy derivatives have been prepared from chlorophyll (alpha) , and their potential photosensitizing ability for the photodynamic therapy of cancer tested in vitro by the MTT assay. The results show that the monohydroxychlorin VI, because of its high photoactivity and its low dark toxicity, is the most promising compound of these series.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The ether-bonded porphyrin-chlorin dimer, that has been synthesized recently in MIFCT as an advantageous second generation photosensitizer, was investigated by steady and time-resolved fluorescence spectroscopy. Chromatography shows that dimer exists as two isomers. Absorption spectra of both isomers are similar and correspond to the overlapping spectra of the initial substances. The fluorescence spectra of isomers differ significantly. While the single fluorescence band of chlorin at 650 nm is typical for the first isomer, the second isomer is characterized by the fluorescence spectrum consisting of three bands at 620, 650, and 685 nm. These data show that there is the energy transfer from porphyrin to chlorin entity. The efficiency of the energy transfer depends on stereometric configuration of dimeric molecules. The results of fluorescence anisotropy measurements confirm the difference in the shape of isomers. The intensive delayed luminescence is an evidence of the existence of long-lived triplet state probably resulting in the high efficiency of singlet oxygen generation.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The strategy for chemical transformation of naturally occurring chlorophylls and bacteriochlorophyll (alpha) has been discussed. The influence of the position and the character of the substitutes on the optical properties was studied. Aminoacid derivatives of purpurin 18 and bacteriopurpurin have been synthesized via direct attachment to propionic acid side chain. Biological trials of chlorin p6 were performed and discussed.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Uptake and phototoxicity of the methyl-, ethyl-, n-propyl, and 2-propyl esters of 132- hydroxy bacteriopheophorbide a were studied in OAT 75 SCLC cells and 3 different amelanotic melanoma cell lines. (A 375, Melur SP 18, SkAMel 25). Specific phototoxicity did not substantially differ for the different esters. Most surprisingly, these photosensitizers did not show any significant threshold behavior: even at 25 (mu) W/cm2 (775 nm, diode laser) cancer cell suspensions were killed in a time-dependent logarithmic fashion. Furthermore, phototoxicity is enhanced at low power densities if compared with the effects at 1 - 10 mW/cm2. This can be related only in part to a lack of oxygen at higher power densities. Complementary experiments confirmed that threshold is power but not dose dependent. Thus, threshold power density should be included into a prospective list of criteria characterizing photosensitizers suitable for photodynamic cancer therapy. The obvious lack of a limiting power density in bacteriopheophobide a esters make these sensitizers a prospective tool for tumor therapy in considerable tissue depth.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Novel porphyrinoid photosensitizers are currently being considered for use in photodynamic therapy (PDT) of cancer. This class of sensitizers combines high absorption characteristics at the therapeutic wavelengths ((lambda) > 600 nm) and good tumor targeting properties. We have investigated the in-vivo uptake and photodynamic damage of several porphycenes. Our model system was the chick chorioallantoic membrane (CAM) which we have adapted for use in PDT studies. The CAM assay allows fast screening of novel drugs and obtaining statistically relevant results with minute quantities of the drug. Sensitizers were `trapped' in EPC (egg phosphatidylcholine) or in DPPC (dipalmitoyl phosphatidylcholine); their efficiencies were independent of the vehicle used for application of the sensitizer. The efficiencies of various porphycenes in PDT, as a function of drug and light dose, compare well with those of standard porphyrins and phthalocyanines.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Benzoporphyrin derivative monoacid ring A (BPD-MA) is a potent new photosensitizer with a significant extinction coefficient at 690 nm. In this study, the photosensitizing efficacy of BPD-MA irradiated at 694 nm with continuous wave (cw) radiation from an argon ion laser pumped dye laser and high intensity pulsed radiation from a ruby laser was compared. Human bladder carcinoma cells in vitro were treated with 0.14 (mu) M BPD-MA for 3 h, washed, then irradiated with either cw or pulsed irradiation. A cumulative cw radiant exposure of 1 or 3 J/cm2 led to cellular survival rates of 38% and 6% respectively compared to untreated controls. Essentially no phototoxicity was observed at the high intensity pulsed powers used in this study.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Laser induced fluorescence spectroscopy (LIFS) was used to detect the presence of PHOTOFRINR porfimer sodium and Benzoporphyrin derivative-monoacid, ring A (BPD-MA) in various tissues. Lobund Wistar rats (n equals 49) inoculated with rat prostatic adenocarcinoma (PA-III) were injected with PHOTOFRINR porfimer sodium (7.5 - 0.25 mg/kg) and BPD (0.50 - 25 mg/kg) intravenously. A Helium-Cadmium laser (442 nm) was used as an excitation source. Our study showed that the amount of PHOTOFRINR porfimer sodium and BPD-MA which localizes in the metastatic lymph nodes is higher than in tumor and all other healthy tissues. Laser induced fluorescence spectroscopy may be a feasible method to detect the distribution of photosensitizers or other fluorescent compounds in vivo.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The purpose of these studies was to determine whether liposomes can deliver the photo- sensitizer TMHP to human bladder carcinoma cells and fibroblast cells, and how effective the photodynamic activity of this photosensitizer is. TMHP was incorporated into small unilamellar liposomes of DPPC. Cellular uptake of TMHP was estimated after extraction with 0.1 N NaOH and by using a fluorescence microscope. Quantitative levels of TMHP in the three cell lines have been expressed in terms of (mu) g per 1.106 cells. PDT was performed for one hour after sensitization using an argon-pumped dye laser at 630 nm. Compared to the fibroblasts, neither a selective uptake of TMHP nor an increased effect of phototoxicity did occur in the tumor cell lines. PDT efficiency is dependent on cell line, dose and fluence rate.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Highly phosphorescent photosensitizer Pd-tetra (o-methoxy-p-sulfo)phenyl porphyrin (Pd- MSPP) was used to follow primary events of photodynamic therapy (PDT). The sensitizer forms complexes with proteins in solutions and biosystems showing remarkable hypsochromic shifts of band and an increase of the quantum yield and life time of phosphorescence at the binding to proteins. It was found the life time of phosphorescence depends mostly on the energy of the lower triplet state of the sensitizer. Therefore photo-chemical quenching of the triplets by cell components is negligible. The quenching of the sensitizer triplets is observed in the presence of free oxygen in biosystems. The degree of quenching varies in dependence on the kind and state of the system and is governed by oxygen concentration and viscosity of the media. It was concluded that the singlet oxygen mechanism of photosensitization is operative only at the primary step of the process.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Interactions of photodynamic sensitizers with cells and tissues
Systemically injected porphyrins and other tetrapyrrolic compounds associate with serum proteins. Highly hydrophobic photosensitizers are mainly associated with lipoproteins and are deposited in intracellular loci of the neoplastic tissue. Hydrophilic photosensitizers are preferentially bound by serum albumin that releases the dye in the vascular stroma of the tumor. As a consequence the type of photosensitizer carrier determines different mechanisms of PDT-induced tumor necrosis. Low-density lipoproteins (LDL) may increase the selectivity of tumor targeting by releasing the bound dye to the neoplastic cells by a receptor-mediated endocytotic mechanism.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Various microscopic methods were established to measure the subcellular distribution and light-induced reactions of photosensitizing porphyrins. These methods include high resolution video microscopy, microspectrofluorometry, as well as time-resolved and time-gated fluorescence spectroscopy. By using these techniques, different components of hydrophylic and hydrophobic photosensitizers (e.g. monomers, aggregates, ionic species) were localized, and their intracellular reactions -- re-distribution, formation of photoproducts, pH-dependent spectral changes -- were studied.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The effect of sulfonations on the PDT efficiency of aluminum phthalocyanines and meso- tetraphenylporphines was studied in the CaD2 mouse mammary carcinoma. The PDT efficiencies were found to decrease in the following order: AlPCS2 > AlPCS4 > Photofrin > TPPS2a > AlPCS1 > TPPS4 > TPPS2o > TPPS1. Apparently, the degree of sulfonations of both families of dyes strongly affects the photobiological properties. It was found to be of great importance whether the sulfonate groups were located adjacently or opposite positions on the molecules.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Since immunity is important in the control of tumor growth and spreading, in our laboratory we examine the effect of photoactivated phthalocyanines on the immune compartment. Spleen hyperplasia as well as spleen and marrow hypercellularities were observed in mice bearing MS-2 fibrosarcoma treated at different times with Aluminum disulfonated Phthalocyanine and laser light. Results suggest a potential `tumor immunity' induced by PDT with photoactivated phthalocyanines and that the dyes used in PDT could play an immunopharmacological role in cancer treatment.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The mechanisms of photoinactivation of NHIK 3025 cells in culture sensitized by sulfonated tetraphenyl porphines (TPPSn) are described. Di- and tetrasulfonated species are mainly located in lysosomes. TPPS1 is located diffusely in the extranuclear space, supposedly bound to endoplasmic reticulum as indicated by electron microscopical findings, and to some extent in lysosomes. After PDT TPPSn penetrates the lysosomal membrane. However, after exposure of cells to TPPS4 and light lysosomal enzymes are inactivated before they eventually can be released to the cytosol. In all cases electron microscopical studies show swollen secondary lysosomes after PDT. TPPSn and light induce accumulation of cells in mitosis. This is due to photochemical damage to the unpolymerized form of tubulin.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The mechanisms of photosensitized tumor destruction during photodynamic therapy (PDT) appear to be a complex interplay of processes involving several tissular components, such as malignant cells, microvasculature, specific blood constituents and non-vascular stroma. While vascular aberrations are of major importance when PDT is performed with Photofrin II, which is the photosensitizer most frequently used in clinical PDT, the initial pattern of tumor damage can be substantially modified by factors that alter the distribution of the photosensitizer in the neoplastic tissue. Such factors include the chemical structure of the photosensitizer, its physico-chemical properties (especially, the degree of hydrophobicity), the modality of its transport in the bloodstream, and the use of delivery systems.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Benzoporphyrin derivative monoacid ring A (BPD) is taken up rapidly (within 30 minutes) by most cells. Rapidly dividing tumor cell lines and mitogen activated murine T lymphocytes were found to take up significantly more (5 - 10 fold) BPD than do normal splenic lymphocytes making them a potential PDT target. Experiments have shown that BPD can be activated in the blood of animals by whole body irradiation with red light, shortly after intravenous administration, in the absence of skin photosensitivity. During the treatment time, plasma levels of BPD were between 0.7 and 1.0 (mu) g/mL. The light treatment resulted in between 70 and 80% photoinactivation of circulating BPD. When L1210 tumor cells were preincubated with BPD and injected i.v. into mice immediately before total body light treatment, significant reductions in circulating clonogenic tumor cells were observed in blood samples taken immediately following treatment. This `transdermal' treatment has been shown to be effective in preventing the development of hind limb arthritis in MRL/1pr mice.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
In order to photosensitize Gram (-) bacteria such as Pseudomonas aeuruginosa and Escherichia coli, we introduced the small peptide polymyxin-B nona-peptide (PBNP) which stimulated the translocation of porphyrin through the outer membrane of these bacteria and makes PDT possible. Gram negative cell killing by the use of PBNP and DP broadens the antibacterial spectrum of photodynamic inactivation and opens new horizons for this modality as a wide spectrum drug when antibiotic resistance is the main concern. Plasmidial and chromosomal DNA damage in S. aureus and E. coli cells was mediated by DP photosensitization. The major observation was the disappearance of the plasmid supercoiled fraction. The chromosomal DNA was also affected and its degradation products were detected after treatment.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The feasibility of using merocyanine 540 (MC 540) and Photofrin II (PII) as effective photodynamic therapeutic (PDT) agents for killing hepatoma cells and duck hepatitis B virus (DHBV) in vitro was investigated. Cultured duck hepatocytes infected with DHBV and hepatoma cells, Hep 3B and HCC 36, were used as models. MC 540 and PII effectively inhibits the DHBV growth by 90 - 99% in a dose- and light-dependent manner. Photodynamic killing of MC 540 in the two hepatoma cell lines results in 94 - 99% growth inhibition. However, both photosensitizers exhibit dark cytotoxicity (37 - 56%). The present results suggest that MC 540 and PII could be promising and effective photodynamic agents for killing HBV and hepatoma cells.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
For the first time a method is proposed for targeted destruction of viral particles with a photoimmuno-toxin. The photoinununotoxin is a conjugate of antibodies and dimethoxy haematoporphyrin (a potent singlet oxygen generator), binding with the viral particle and upon illumination with visible light inactivating the virus by singlet oxygen. The method can be used to combat viral infection in humans and to prevent lysis of industrial micro-organisms by lysogenic bacteriophage strains.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
A new photosensitizer (PS), meso-tetrahydroxyphenyl-chlorin(m-THPC), has been clinically evaluated for photodynamic therapy (PDT) of early squamous cell carcinomas located in the upper aerodigestive tract, the oesophagus and the tracheobronchial tree. The injected doses ranged between 0.1 - 0.3 mg/kg m-THPC and the wavelength of the excitation light was either at 514 nm or 652 nm. The evaluation of the m-THPC induced phototoxicity was carried out on healthy mucosae of the bronchi, the oral cavity and the skin, using various `frontal' light distributors. Skin photosensitization tests were performed with a filtered Xenon white light source which simulates the solar emission spectrum at noon on a clear summer day at sea level at our latitude. At the present time, we are still searching for conditions where effective PDT with m-THPC of early carcinomas of the upper aerodigestive tract, the oesophagus and the tracheobronchial tree would show a real selectivity, i.e., destruction of the neoplastic tissue without necrosis of the surrounding normal tissue.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
A new photosensitizer (PS), meso-tetrahydroxyphenyl-chlorin(m-THPC), has been clinically evaluated for photodynamic therapy (PDT) of early squamous cell carcinomas located in the upper aerodigestive tract, the oesophagus and the tracheobronchial tree. The injected doses ranged between 0.1 - 0.3 mg/kg m-THPC and the wavelength of the excitation light was either at 514 nm or 652 nm. The evaluation of the m-THPC induced phototoxicity was carried out on healthy mucosae of the bronchi, the oral cavity and the skone cell population to the other. Appearance of aneuploid populations after PDT suggests that destruction of sensitive cell populations allows the growth of initially non FCM detectable aneuploid clones. MDA assay could thus be a good prognostic tool although larger series of patients are needed. 115
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Since 1976, photodynamic therapy (PDT) has been used for the treatment of different stages of urothelial bladder tumors. First applications were based on the irradiation of single exophytic tumors using bare fibers for laser irradiation (630 mm) or bright white light generated e.g. from a mercury arc lamp. Clinical results of several centers demonstrated the possibility of destroying single superficially growing tumors. A new approach to the treatment of multifocal growing tumors, including the endoscopically often undetectable carcinoma in situ, was provided by the development of treatment modalities allowing for whole bladder wall irradiation. Photodynamic diagnosis (PDD) is a novel procedure for detecting flat precancerous and malignant lesions undetectable by endoscopy alone on the basis of laser- induced fluorescence.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The induction of protoporphyrin (PP) synthesis in B16 melanoma cells and their subsequent photodestruction was investigated. Photosensitized cells gradually disintegrated following prolonged irradiation. The photosensitized cells showed an immediate potassium loss compensated only partially by influx of Na and other ions. The dominant characteristics of these cells were potassium efflux, water influx and ultrastructural damage in subcellular compartments. In conclusion, a highly efficient system for killing B16 melanoma cells was achieved by photosensitization of endogenous PP produced subsequent to chemical induction.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Protoporphyrin-dimethylester (PP) is an amphiphilic porphyrin which shows a fast clearance and is therefore of interest for photodynamic therapy. The localization of the sensitizer is one point of interest, since it has a strong influence on the phototoxic effect. Localization of PP in fibrosarcoma cells was probed by time resolved and steady state spectroscopy. Dioleoyl L- (alpha) -phosphatidylcholine (DOPC) liposomes were used as a carrier system for the amphiphilic sensitizer with a molar ratio of PP/DMSO equals 1/200. Since intermembrane exchange is responsible for the uptake of PP we expected a membrane bound localization. Therefore the characterization of the microenvironment was based on the comparison of the spectroscopic properties of PP in organic solvents, artificial membranes and in cells. Based on this comparison we suggest that PP is bound within the amphiphilic part of the membranes i.e. between the polar headgroups and the fatty acyl chains of the cytoplasm membrane.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Photodynamic therapy (PDT) is a treatment modality for a variety of cancers. Since no ideal photosensitizer is available yet, new photosensitizers are being sought. A new concept of PDT is the use of endogenous photosensitizers. ALA is a metabolite in heme synthesis. It is a precursor of protoporphyrin IX, a potent photosensitizer. After administration of ALA it is transformed by the cells to protoporphyrin IX. The goal of our study was to examine dark toxicity of ALA and its phototoxic potential in two different human cell lines.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Hydrophobic photosensitizers readily intercalate into plasma lipoproteins. Some tumors acquire cholesterol from the circulation as a result of increased low density lipoprotein (LDL) receptor activity. Thus, circulating LDL may function as a vehicle for the delivery of bound Zn-Pc to cells within a tumor. Zn-Pc:LDL complexes, resulting from the interaction of LDL with the liposomal Zn-Pc formulation CGP55847, bind to the LDL receptor expressed on HepG2 cells but with reduced affinity in comparison to LDL. Confocal fluorescence microscopy facilitated the subcellular localization of Zn-Pc in microcolonies of HepG2 cells; the photosensitizer was distributed throughout the cellular membrane systems but was absent from the cell nucleus. Uptake of Zn-Pc in the presence of LDL was twofold greater than in the absence of the lipoprotein. These data suggest that the LDL uptake pathway may contribute to the localization of Zn-Pc in hyperproliferative tissue.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Photofrin levels in different cellular populations constituting a murine FsaR fibrosarcoma were measured by flow cytometry. Both myeloid and lymphoid populations associated with the tumor were found to accumulate more photosensitizer on a per cell basis, on average, than the malignant cells. Macrophages, identified by the F4/80 antigen, exceeded other myeloid cells in Photofrin accumulation. It is shown that one of the factors involved is the variability in the photosensitizer content in cells located at different distances from the nearest blood vessel. This was investigated by a flow cytometry technique with the fluorescent stain Hoechst 33342, used to distinguish cells depending on their proximity to the tumor vasculature.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Liposomes were prepared containing zinc-phthalocyanine (ZnPc). The composition was ZnPc/POPC/OOPS (1:90:10 w/w /w). The phospholipids (PL) were dissolved in t-butanol at 50 degree(s)C under magnetic stirring and mixed with ZnPc, dissolved in NMP for two hours in an ultrasonic bath at 80 degree(s)C. This mixture (50 degree(s)C) was diluted with lactose- NaCl solution (9.475% lactose, 0.027% NaCl) at 4 degree(s)C using a dynamic mixer. The collected liposomal suspension was concentrated first, to 20 mg PL/ml suspension and then the organic solvents were removed by tangential flow filtration (CentrasetteR) against a ten fold volume of lactose-NaCl solution. After sterile filtration the liposomal suspension was freeze-dried for 24 hours.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The kinetics of cellular damage after photodynamic action was studied by means of flow- cytometry. Cultured K562 cells were loaded with tetrasulphonated aluminum phthalocyanine and propidium iodide, acridine orange and rhodamine 123 were used to assess the damage done to the cells. Exposure of phthalocyanine-loaded cells to light resulted in the following order of events: increase of the intracellular Pc fluorescence -> mitochondrial damage -> changes of the cell surface and/or volume -> plasma membrane potential vanishing -> severe damage of cell plasma membrane. For all these processes it takes approximately two hours to reach the stationary state.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
A new modality of interstitial therapy to treat prostate cancer using photodynamic principles has been studied in a canine model. The effect of interstitial application of monochromatic light from an argon pumped dye laser at 630 nm was studied in a canine model. No significant hyperthermia was seen during the treatment. A concentric zone around the treatment fiber was seen during the treatment. A concentric zone around the treatment fiber was seen in PDT treated dogs and the maximum size was 18 mm. The data suggests that PDT may be clinically applicable in achieving tissue necrosis using interstitial light application in a solid organ like prostate.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Photosensitizing drugs (e.g. porphyrins) are likely to be degraded upon irradiation. The mechanisms of photodegradation are complex. The photodegradation behavior of photosensitizers used in photodynamic therapy (PDT) could be used as a tool for dosimetry and for protecting adjacent tissue against photodynamic effects. The photobleaching behavior of (delta) -aminolevulinic acid induced porphyrins has been studied. The results of in vitro experiments (Protoporphyrin IX in organic solvent) and the in vivo tests (SSK2-fibrosarcoma on C3H-mice) have shown the bleaching rate to be dependent on the environment of the photosensitizer. During its photodegradation a chlorine-type photoproduct is formed. Its spectrometric detection reveals on signals proposed for dosimetry in PDT.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The pharmacokinetics of 132-hydroxy-bacteriopheophorbide a methyl ester (OH-BPME) was studied on Lewis lung carcinoma bearing mice by fluorescence spectroscopy. The sensitizer distribution in different organs and in the tumor was investigated in dependence on the incubation time. A very fast cleaning of the blood and the skin was observed. The results of our investigations suggest that PDT using OH-BPME could be effective at sensitizer incubation times of about 12 h.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
PDT and on-line fluorescence spectroscopy were carried out on human tumors after ALA- administration using 633 nm-light of a dye laser as therapeutic radiation and as fluorescence excitation radiation. This has the following advantages: (1) use of one laser for PDT and fluorescence diagnosis only, (2) the possibility of on-line fluorescence measurements, and (3) excitation of protoporphyrin molecules in deep tissue layers. Monte Carlo calculations were carried out to determine the excitation and fluorescence photon distribution in the case of red and violet excitation radiation. The results show the possibility of depth-resolved measurements on the fluorophore distribution by variation of the excitation wavelength. The influence of remitted excitation light and of the spontaneous radiation from the laser as well as the possible excitation of food-based degradation products of chlorophyll has to be considered in high-sensitive fluorescence measurements.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Efficiency of cell radiosensitization by porphyrins is a function of the irradiation dose, the nature of the cell and physico-chemical properties of the sensitizer. The maximal radio- sensitization for E. ascites tumor cells was reached at 2 Gy, for Saccharomyces cerevisiae- 25Gy. The radiosensitization by different porphyrins in E.ascites tumor cells increases their cytotoxicity by a factor of 3, in Saccharomyces cerevisae --inhibition of growth 0.5 - 2.5 time.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
A series of new octakis-substituted Germanium-phthalocyanines for use in photodynamic therapy of tumors has been synthesized. Starting from 1,4-dialkoxy-2,3-dicyano-benzene the metal-free octakis-alkoxy-phthalocyanine 13 was prepared. The metallation to the corresponding octakis-alkoxy-GeCl2-phthalocyanine 15 was done with a GeCl4-DMF complex. Alkaline hydrolysis gave quantitatively the octakis-alkoxy-Ge(OH)2- phthalocyanine 16. By substitution of the hydroxy groups with alcohols, thiols and silanols the axially disubstituted phthalocyanines were obtained. The most important photophysical properties for PDT (Q-bands, singlet oxygen quantum yields and (Phi) f) are reported.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Zinc-(II)-phthalocyanine (ZnPc) is a drug that can potentially be used in photodynamic therapy. A promising formulation approach for the strongly hydrophobic ZnPc is to embed the molecule in liposomes. CGP 55847 is such a liposomal ZnPc formulation. From our data, we could conclude that approximately one quarter of the drug molecules were only loosely bound to the liposomes and exchanged between them with a relaxation time of about 15 min. Energy transfer measurements before and after the lyophilization process revealed that the liposomes were stable when suspended in a 10% lactose solution, i.e. no fusion of liposomes took place. In aqueous solution, however, lyophilization induced fusion of liposomes to a small extent with a concomitant increase in size.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Tetrasulphonated aluminum phthalocyanine (AlPcS4) is one of the extensively studied second generation sensitizers for photodynamic therapy of cancer. We've applied picosecond fluorescence spectroscopy to study the fluorescence decay lifetimes of AlPcS4 in phosphate buffer at different pH values and in monolayers of cultured cells incubated in photosensitizer solution. The decay time for the cells in the buffer is closer to the one obtained for acidic aqueous solution indicating that at least part of the phthalocyanine could be found in the acidic microenvironment (lysosomes, etc.).
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The photophysics of sulphonated aluminum phthalocyanines, AlPcSn (n equals 0, 1, 2, 3 or 4), potential second-generation phototherapeutic agents for tumors, in cationic reversed micelles of benzyl ammonium hexadecyl chloride (BHDC) and anionic reversed micelles of sodium di(2-ethylhexyl) sulphosuccinate (AOT) have been investigated. Absorption spectroscopy, as well as steady state and time-resolved fluorescence emission studies, indicate that in BHDC the di- and tri-sulphonated derivatives are essentially monomeric whereas in AOT only the di-sulphonated phthalocyanine was found to be monomeric. The distribution of AlPcSn in the reversed micelles, which appears to be strongly influenced by the extent of sulphonation and the environment of the reversed micelle, is discussed. It is anticipated that extrapolation can then be made to heterogeneous systems such as are found in biomembranes.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Laser induced localized temperature distribution control in tissue could for instance provide in the targeted (e.g. tumor) area maximum sets of values to be used in efficacy increase for photodynamic therapy (PD) and hyperthermia (HT) applications. Spatial temperature distribution calculation method based on analytical solution of heat transfer equation is presented for laser induced heating and external tissue surface cooling combination. This method was applied to provide maximum temperature increase in deep tissue layers. Analytical relations for laser beam parameters and temperature threshold diagrams are obtained. These diagrams are to be used to avoid tissue burn. Examples of temperature increase in deep tissue layers are presented.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The possibility of using photosensitizers, working in the near-IR range, affords new perspectives on their use in diagnosis and treatment of diseases such as cancer and atherosclerosis. Photosensitizers whose absorption spectrum maximum corresponds to laser wavelengths represent the most interest. The most interesting exploitation of photosensitizers is in the rechannelization of respiratory airways and gullet in the presence of a large malignancy. In this case, the joint action of high-intensity irradiation and possibly PDT can help prevent metastasis. The synthesis and investigation of spectroscopic properties of near-IR-range photosensitizers is of great importance.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The first experience of photodynamic therapy (PDT) in Russia is presented. Thirty-three patients have been treated by PDT since February 1992 with a photosensitizer from the hematoporphirine group -- Photogem. The follow-up results (5th - 18th months) have been controlled in all patients with skin cancer and basalioma, cancer of the tongue, lower lip and oral mucous, breast cancer, lung cancer and tumor of other locations. Positive effect has been observed in 30 patients (90.9%). Total regression of the tumor was seen in 16 patients (48.5%) and partial reduction -- in 14 cases (42.4%).
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Photochemical reactions under the action of powerful ultrashort laser pulses occur with excitation of sensitizers to high lying singlet and triplet states can be quite different from those occurring from S1 and T1 and in some cases have greater photochemical and photobiological efficiency in vivo and in vitro. In our paper we are modelling the primary photoprocesses in hematoporphyrin molecules under the excitation by cw and pulsed light. On the basis of the proposed theoretical model the pulse duration and intensity region, where photobleaching of ground state absorption and absorption from exited singlet and triplet states have influence on the type II photodynamic processes, was estimated. The results show that Hp ground state bleaching and the efficiency of photodynamic therapy is reduced when the pulse energy is over the value 10 mJ/cm2. The dependence of the efficiency of the photochemistry from triplet state on laser pulse intensity and duration was studied. The published results of some PDT experiments in comparison with efficiency curve based on our model are presented.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
A phthalocyanine derivative with two cholesterol moieties as axial ligands to the central Ge(IV) ion efficiently photosensitizes the oxidative modification of L-tryptophan. Administration of liposome-bound GePc to Balb/c mice bearing a MS-2 fibrosarcoma yields a quantitative release of the dye to serum lipoproteins, followed by a selective accumulation in the tumor as well as a low content in the skin. At 24 h after injection of 0.76 mg/kg GePc, the tumor was irradiated with 600 - 700 nm light; tumor necrosis appeared in all treated mice as a consequence of extensive damage of cellular and stromal elements.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The experimental approach which confirmed the participation of singlet oxygen in the photosensitization of green alga Dunaliella is proposed.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Athymic nude mice with subcutaneously xenotransplanted urothelial carcinoma received intravenously injections of the synthetic sensitizer meso-tetra (4-carboxyphenyl) porphyrin. Fluorescence at the tumors and the skin was excited using a Kr+ laser (407 nm) and was detected at 652 nm using a fiberoptical sensor in combination with an optical multichannel analyzer at different times after application of the sensitizer. Photodynamic treatment was carried out using an Ar+ laser pumped dye laser (650 nm; 100 mW/cm2; 100 J/cm2). The delay of tumor growth was determined in a follow-up period of four weeks and was correlated to the in vivo fluorescence measurements.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Suitable methods for synthesis of water soluble diphthalocyanines of rare earth elements have been developed. The synthesis was carried out by direct sulphonation of corresponding unsubstituted analogues. The sulphonation degree depends on the nature of a sulphonated agent, reaction time and molecular ratio of reagents. This allows us to vary the number of sulpho groups from one to the values corresponding to full sulphonation.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The introduction of sulpho groups into molecule of mono- and diphthalocyanines of hafnium and zirconium gave rise to the formation of water soluble compounds. This allows us to extend the field of their applications. The dyes of this class have been found to be efficient photosensitizers for PDT of cancer.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Width of the therapeutic action of a drug model on the basis of aluminum sylphonated phthalocyanine -- photosensitizer of the second generation for PDT -- was investigated on laboratory mice with spontaneous breast tumor. Three general types of tumors were investigated in the process of morphological investigation: pleomorphic adenocarcinomas of type A and B, and monomorphic adenocarcinomas of type C. Different tumors local selectivity to the present photosensitizer was established by the microspectrofluorimetric method. The largest tumor accumulation selectivity, and also photosensitizer distribution uniformity, were revealed in a high-differentiation variant of pleomorphic adenocarcinomas of type B, which is more sensitive to PDT. It was experimentally determined that the combination of surface and interstitial irradiation is necessary in the overwhelming majority of cases.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Fluorescence colocalization with the Golgi specific stain, NBD-ceramide, and the mitochondrial localizing stain, Rhodamine 123, confirmed the earlier assumption that the Golgi apparatus is one of the prominent storage compartments for bacteriopheophorbide esters in OAT 75 SCLC cells and several amelanotic melanoma cell lines (A375, Melur SP18, SkAMel 25). Furthermore, a diffuse staining of mitochondria, of non-structured cytoplasm, and an additional storage in melanine vesicles of the amelanotic melanoma cells suggests further storage compartments with quantitatively different contributions to the phototoxicity of bacteriochlorophyll-derived photosensitizers. Independent observations of early phototoxic effects on microfilamentous networks, enzymatic activities (succinate dehydrogenase, lactate dehydrogenase), and redistribution phenomena following primary uptake of the sensitizers let us assume that only a part of the 108 molecules taken up by a cell contribute directly to phototoxicity. Thus it may be asked if a proper subcellular positioning of only a few sensitizer molecules may have similar phototoxic effects as the huge amounts stored at apparently ineffective sites.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
An octakis-decyl-substituted Zn(II)-phthalocyanine (ZnODPc) was prepared by chemical synthesis and was shown to possess favorable photophysical properties to act as a photodynamic agent. Intravenous injection of ZnODPc incorporated into Cremophor emulsions (1.2 or 2.4 mg/kg) to Balb/c mice bearing a MS-2 fibrosarcoma resulted in an efficient and selective accumulation of the phthalocyanine in the tumor. Illumination of the ZnODPc-loaded neoplastic lesion at 24 h after injection caused tumor regression as a result of both intracellular and intravascular damage.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Experiments were performed on five batches of Wistar inbred rats with Walker-256 carcinosarcoma receiving sole treatment photodynamic therapy (PDT), irradiated endotoxin (R-LPS), native-endotoxin (N-LPS), or associated therapy (PDT + R-LPS) and the control batch (saline) consisted of animals with untreated Walker-256 tumors. The results were as follows: the sole treatment (PDT, R-LPS, N-LPS) gave survival rates between 56.3 and 60.7% and cure rates ranging from 32.1 to 37.5%. The `combined' therapy in multiple doses increased significantly (88.6%) the survival rate of tumor bearing rats as well as the highest incidence of complete tumor regression (71.4%). This work demonstrates that `combined' photodynamic and immunotherapy with irradiated endotoxin stimulates cell-mediated antitumoral activity and induces changes in the tumoral incidence in Walker-256 carcinosarcoma in the rat model.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
An outstanding problem in clinical photodynamic therapy (PDT) of cancer is the application of experimental and previous case studies to the prediction of doses and treatment regimes. The problem derives partly from the fact that several sets of data are incomplete and are not accessible during the course of the treatment of an individual patient. The objective of the computer database project is to provide an enabling utility to support decision making and also to analyze objectively pharmacokinetic, chemical pathological and clinical data with a view to identifying previously unrecognized correlations. The database has been initially developed using a data set from a number of clinical studies to assess the pharmacokinetic profiles of the PDT agents being used. It can be used to create a PDT treatment advice knowledge based system, relating to useful treatment strategies for PDT, and insights into areas of research in terms of isolating critical parameters of PDT.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
We developed a Monte Carlo model to estimate the light distribution in tissue. The underlying assumption of the calculation is the knowledge of the microscopic tissue optical parameters. In the simulation we start with a single point illumination in a 3-D multi-layer tissue model. To get the light distribution for extensive irradiation we convolve the `single point solution' with the expanded irradiance profile. The aim of our simulation is the development and design of diverse PDT-applicators for dosimetry reasons and as an inverse method, the calculation of microscopic tissue optical parameters for different tumor samples from ex vivo measurements.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
For safe light dosimetry in photodynamic therapy (PDT) in organs like the oesophagus, the knowledge of the space irradiance distribution in tissue is especially important. In order to obtain this distribution we are studying two methods which are being evaluated in a clinical environment. The first method is non invasive and is based on the measurement of optical tissue parameters. For this measurement, several types of optical probe have been developed. The second method is invasive and measures light in situ by means of an optical fiber probe with a fluorescent tip. Together with these measuring techniques and results we present some simple notions of light dosimetry which can be used to improve the safety and the efficacy of the clinical PDT.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Photodynamic therapy has been used for treatment of malignant cutaneous lesions. Photosensitizer has been topically applied, 5-aminolevulinic acid, with light delivered at 630 nm. A study of response rate to varying light doses was performed, it might seem that light doses of 40 - 50 J/cm2 is sufficient for superficial lesions. For nodular lesions higher light doses are needed. Some patients with tumors in the gastrointestinal tract have been treated with systemic administration of 5-aminolevulinic acid and re-treated with Photofrin in case of unsatisfactory results. From the preliminary material available 5-aminolevulinic acid seems less promising as a photosensitizer for internal lesions compared to dermal lesions.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The depth distribution of 630 nm laser light has been measured for ten patients during the photodynamic therapy of skin lesions by the application of topical 5-aminolaevulinic acid followed by surface illumination. Results show that the light distribution can be described by the diffusion theory. The values of effective attenuation coefficient obtained for each lesion are in close agreement (0.352 mm-1 +/- 8%) but the K value, used to describe sub-surface fluence build-up, varies between 0.12 and 8.23, although similar values are obtained for the same type of lesion.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The use of photodynamic therapy in the removal of the endometrial layer of the uterus provides the possibility of a rapid and effective treatment of menorrhagia avoiding the difficulties and complications of conventional methods. A treatment is proposed in which topical application of 5-aminolaevulinic acid to the inner surface of the uterus is followed by illumination at 630 nm. The surface layer would in this way be rendered necrotic to slough off over subsequent days. The removal of the entire endometrium must be achieved in order to prevent the return of the original condition, which demands that a therapeutic dose of both light and photosensitizer must be achieved throughout the depth of the tissue. This work presents a method of light delivery suitable for intra-uterine PDT along with in vitro optical phantom and ex vivo tissue measurements that aid in the characterization of the light field prior to treatment. These measurements allow the prediction of a treatment time suitable for the delivery of an effective light dose.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Photodynamic therapy (PDT) of tumors in the urinary bladder requires a homogeneous light distribution on the whole organ wall. The light applicator recently developed consists of a catheter-supported isotropic emitter and a concentric outer balloon, which guarantees a centric position. For dosimetry a detector fiber with conical end is axially placed half way between center and bladder outlet. It detects the light backscattered from the bladder wall. It has been tested by means of a bladder phantom model with variable backscattering properties. To study the limits of this irradiation and dosimetry concept in case of nonspherical bladder shapes the light distributions in hollow ellipsoids with backscattering surface have been investigated by computer simulation. It shows that the ratio of the largest to the smallest fluence rate and the ratio of the largest to the smallest diameter of the bladder are nearly equal.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The optical absorption, scattering and anisotropy coefficient of piglet and diseased human bladder tissue were determined in vitro in the wavelength range of 500 - 650 nm. Monte Carlo simulations for whole bladder wall (WBW) photodynamic therapy (PDT) have been performed using the optical parameters determined in vitro. The calculated light dose rate values are in agreement with those measured in clinical WBW-PDT, previously performed at 630 nm. The light dose rate at the bladder wall can differ by a factor of 4, due to variations in optical properties of the tissue. This demonstrates the necessity of in situ light dosimetry during clinical WBW-PDT. WBW-PDT with red light (630 nm) will be technically more advantageous than with green light (532 nm), because of a higher integrating sphere effect.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
When measuring laser light distribution in tissue during photodynamic therapy, accurate determination of the position of the monitoring probes is vital. For this purpose, computerized tomographic scanning has been incorporated into our treatment routine. Different mixtures of barium sulphate powder and an opaque dental sealant were used in the construction of probes which could be imaged on a computerized tomographic scan. These were tested for radio- opacity, isotropy and strength, and a mixture of 27% barium sulphate powder and 73% opaque dental sealant was found to be suitable.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
After clinical photodynamic therapy (PDT) and radiotherapy (RT) of the colon carcinoma acute and late damages on adjacent normal tissue were seen. Therefore it was the aim of this experimental study to investigate these damages on normal colon tissue of rats after PDT in comparison with RT. Within the first hours after PDT the endoscopic examination showed a severe acute damage. The histopathological examination showed that the acute ulceration depends on the energy density applied within the first three days. This study indicates different progresses of acute effects after PDT and RT, respectively. Late damages were observed only by RT in contrast to PDT. Synthetic diet prevents acute damages after PDT. However, the synthetic diet after RT can prevent the late damage for the duration of the diet administration.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.