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Cancers Jul 2023To overcome the poor prognosis of cholangiocarcinoma (CCA), highly targeted therapies, such as antibody-drug conjugates (ADCs), photodynamic therapy (PDT) with/without... (Review)
Review
To overcome the poor prognosis of cholangiocarcinoma (CCA), highly targeted therapies, such as antibody-drug conjugates (ADCs), photodynamic therapy (PDT) with/without systemic chemotherapy, and experimental photoimmunotherapy (PIT), have been developed. Three preclinical trials have investigated the use of ADCs targeting specific antigens, namely HER2, MUC1, and glypican-1 (GPC1), for CCA. Trastuzumab emtansine demonstrated higher antiproliferative activity in CCA cells expressing higher levels of HER2. Similarly, "staphylococcal enterotoxin A-MUC1 antibody" and "anti-GPC1 antibody-monomethyl auristatin F" conjugates showed anticancer activity. PDT is effective in areas where appropriate photosensitizers and light coexist. Its mechanism involves photosensitizer excitation and subsequent reactive oxygen species production in cancer cells upon irradiation. Hematoporphyrin derivatives, temoporfin, phthalocyanine-4, talaporfin, and chlorine e6 derivatives have mainly been used clinically and preclinically in bile duct cancer. Currently, new forms of photosensitizers with nanotechnology and novel irradiation catheters are being developed. PIT is the most novel anti-cancer therapy developed in 2011 that selectively kills targeted cancer cells using a unique photosensitizer called "IR700" conjugated with an antibody specific for cancer cells. PIT is currently in the early stages of development for identifying appropriate CCA cell targets and irradiation devices. Future human and artificial intelligence collaboration has potential for overcoming challenges related to identifying universal CCA cell targets. This could pave the way for highly targeted therapies for CCA, such as ADC, PDT, and PIT.
PubMed: 37509347
DOI: 10.3390/cancers15143686 -
Frontiers in Surgery 2019The aim of this study was to demonstrate the clinical feasibility of intraoperative photodiagnosis (PD) of malignant brain tumor using talaporfin sodium (TPS), which is...
The aim of this study was to demonstrate the clinical feasibility of intraoperative photodiagnosis (PD) of malignant brain tumor using talaporfin sodium (TPS), which is an agent used in photodynamic therapy (PDT) for cancers. Forty-seven patients diagnosed with malignant gliomas by preoperative imaging (42 patients with gliomas and 5 patients with other brain tumors) received an intravenous injection of TPS at 40 mg/m 24 h before resection. During surgery, these patients were irradiated with diode laser light at 664 nm, and tumor fluorescence was observed. The fluorescence intensity was visually rated on a 3-point rating scale [strong fluorescence, weak fluorescence and no fluorescence]. TPS concentrations in 124 samples from 47 cases were measured by HPLC (High performance liquid chromatography). The fluorescence intensity was confirmed to be weak in all patients with Grade II gliomas and strong in almost all patients with Grade III or IV gliomas, reflecting the histological grade of malignancy. In patients with non-glioma brain tumors except for 1 patient with a metastatic brain tumor, the fluorescence intensity was strong. The mean TPS concentration in tissues was 1.62 μg/g for strong fluorescence areas, 0.67 μg/g for weak fluorescence areas and 0.19 μg/g for no fluorescence areas. Establishment of an appropriate fluorescence observation system enabled fluorescence-guided resection of malignant brain tumors using TPS, and the fluorescence intensity of tumors correlated with the TPS concentrations in tissues. These results suggest that TPS is a useful photosensitizer for both intraoperative fluorescence diagnosis and photodynamic therapy.
PubMed: 30949484
DOI: 10.3389/fsurg.2019.00012 -
Lasers in Surgery and Medicine Oct 2017Alternative treatments are needed to achieve consistent and more complete port wine stain (PWS) removal, especially in darker skin types; photodynamic therapy (PDT) is a...
BACKGROUND AND OBJECTIVE
Alternative treatments are needed to achieve consistent and more complete port wine stain (PWS) removal, especially in darker skin types; photodynamic therapy (PDT) is a promising alternative treatment. To this end, we previously reported on Talaporfin Sodium (TS)-mediated PDT. It is essential to understand treatment tissue effects to design a protocol that will achieve selective vascular injury without ulceration and scarring. The objective of this work is to assess skin changes associated with TS-mediated PDT with clinically relevant treatment parameters.
STUDY DESIGN/MATERIALS AND METHODS
We performed TS (0.75 mg/kg)-mediated PDT (664 nm) on Sprague Dawley rats. Radiant exposures were varied between 15 and 100 J/cm . We took skin biopsies from subjects at 9 hours following PDT. We assessed the degree and depth of vascular and surrounding tissue injury using histology and immunohistochemical staining.
RESULTS
TS-mediated PDT at 0.75 mg/kg combined with 15 and 25 J/cm light doses resulted in vascular injury with minimal epidermal damage. At light dose of 50 J/cm , epidermal damage was noted with vascular injury. At light doses >50 J/cm , both vascular and surrounding tissue injury were observed in the forms of vasculitis, extravasated red blood cells, and coagulative necrosis. Extensive coagulative necrosis involving deeper adnexal structures was observed for 75 and 100 J/cm light doses. Observed depth of injury increased with increasing radiant exposure, although this relationship was not linear.
CONCLUSION
TS-mediated PDT can cause selective vascular injury; however, at higher light doses, significant extra-vascular injury was observed. This information can be used to contribute to design of safe protocols to be used for treatment of cutaneous vascular lesions. Lasers Surg. Med. 49:767-772, 2017. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Lasers, Semiconductor; Male; Photochemotherapy; Photosensitizing Agents; Porphyrins; Port-Wine Stain; Rats; Rats, Sprague-Dawley; Skin
PubMed: 28489260
DOI: 10.1002/lsm.22677 -
Frontiers in Neurology 2018The goal of this study was to demonstrate the feasibility of intraoperative photodynamic diagnosis (PDD) of malignant glioma using the fluorescence from talaporfin...
OBJECTIVE
The goal of this study was to demonstrate the feasibility of intraoperative photodynamic diagnosis (PDD) of malignant glioma using the fluorescence from talaporfin sodium (TS), which is used simultaneously for photodynamic therapy (PDT).
METHODS
Patients with suspected primary malignant glioma who were eligible for surgical removal of the tumor and PDT with TS were enrolled in this prospective study. Tissue samples were obtained from the contrast-enhanced (CE) region and from the surrounding non-contrast-enhanced (NCE) marginal tissue at the boundary between the tumor and normal tissue. The excised samples were set into a fluorescence measurement system, which consisted of a semiconductor laser with a 400-nm wavelength for excitation, and a compact spectrometer for detection, which were applied and received through a custom-made probe consisting of coaxial optical fibers. The fluorescence spectrum was obtained, and peak intensity was calculated. Tumor cellularity was histopathologically analyzed and semi-quantitatively classified into four (0-3) categories.
RESULTS
86 samples from 17 surgical cases were available for fluorescence measurement and analysis. The fluorescence from TS had a single peak at 664 nm that was easily distinguished from the 400-nm excitation light. Samples from the CE regions showed higher fluorescence intensity than those from the NCE regions ( < 0.001). DAPI staining and fluorescence microscopy confirmed that cells in the CE regions showed red fluorescence in their cytoplasm. The fluorescence was notably strong along vascular endothelium. CE samples from newly diagnosed versus recurrent cases showed no difference in fluorescence intensity ( = 0.26). Among all samples (CE and NCE combined), the fluorescence intensity was very high in those of histopathological class 3, and a trend of increased fluorescence according to histopathological class ( < 0.001) was shown. Differences between class 0 and 3 ( < 0.001), class 1 and 3 ( < 0.001), and class 2 and 3 ( = 0.018) were significant.
CONCLUSION
Intraoperative simultaneous PDD and PDT with TS can be performed for patients with malignant glioma. The blue excitation light that is used for 5-aminolevulinic acid PDD can be used for our technique (TS-PDD). The strong fluorescence from pathologically malignant tissues may be due at least in part to the involvement of microvascular structures.
PubMed: 29441040
DOI: 10.3389/fneur.2018.00024 -
The Journal of Toxicological Sciences 2017Photodynamic therapy (PDT) is a Food and Drug Administration authorized method for cancer treatment, which uses photosensitizer and laser photo-irradiation to generate... (Comparative Study)
Comparative Study
Photodynamic therapy (PDT) is a Food and Drug Administration authorized method for cancer treatment, which uses photosensitizer and laser photo-irradiation to generate reactive oxygen species to induce cell death in tumors. Photosensitizers have been progressively developed, from first to third generation, with improvements in cell specificity, reduced side effects and toxicity, increased sensitivity for irradiation and reduced persistence of photosensitizer in healthy cells. These improvements have been achieved by basic comparative experiments between current and novel photosensitizers using cell lines; however, photosensitizers should be carefully evaluated because they may have cell type specificity. In the present study, we compared a third-generation photosensitizer, β-mannose-conjugated chlorin (β-M-chlorin), with the second generation, talaporfin sodium (NPe6), using seven different rat and human cell lines and a neuronal/glial primary culture prepared from rat embryos. NPe6 was more effective than β-M-chlorin in human-derived cell lines, and β-M-chlorin was more effective than NPe6 in rat primary cultures and rat-derived cell lines, except for the rat pheochromocytoma cell line, PC12. These differences of phototoxicity in different cell types are not because of differences in photosensitivity between the photosensitizers, but rather are associated with different distribution and accumulation rates in the different cell types. These data suggest that evaluation of photosensitizers for PDT should be carried out using as large a variety of cell types as possible because each photosensitizer may have cell type specificity.
Topics: Animals; Antineoplastic Agents; Cell Line; Cell Line, Tumor; Cell Survival; Cells, Cultured; Humans; Light; Mannose; Neurons; PC12 Cells; Photochemotherapy; Photosensitizing Agents; Porphyrins; Rats; Rats, Wistar
PubMed: 28070104
DOI: 10.2131/jts.42.111 -
Scientific Reports Apr 2024To investigate the therapeutic potential of photodynamic therapy (PDT) for malignant gliomas arising in unresectable sites, we investigated the effect of tumor tissue...
To investigate the therapeutic potential of photodynamic therapy (PDT) for malignant gliomas arising in unresectable sites, we investigated the effect of tumor tissue damage by interstitial PDT (i-PDT) using talaporfin sodium (TPS) in a mouse glioma model in which C6 glioma cells were implanted subcutaneously. A kinetic study of TPS demonstrated that a dose of 10 mg/kg and 90 min after administration was appropriate dose and timing for i-PDT. Performing i-PDT using a small-diameter plastic optical fiber demonstrated that an irradiation energy density of 100 J/cm or higher was required to achieve therapeutic effects over the entire tumor tissue. The tissue damage induced apoptosis in the area close to the light source, whereas vascular effects, such as fibrin thrombus formation occurred in the area slightly distant from the light source. Furthermore, when irradiating at the same energy density, irradiation at a lower power density for a longer period of time was more effective than irradiation at a higher power density for a shorter time. When performing i-PDT, it is important to consider the rate of delivery of the irradiation light into the tumor tissue and to set irradiation conditions that achieve an optimal balance between cytotoxic and vascular effects.
Topics: Animals; Photochemotherapy; Glioma; Porphyrins; Mice; Lasers, Semiconductor; Cell Line, Tumor; Photosensitizing Agents; Disease Models, Animal; Allografts; Apoptosis; Male
PubMed: 38644422
DOI: 10.1038/s41598-024-59955-y -
Sensors (Basel, Switzerland) May 2015Fluorescence spectra and fluorescence lifetime images of talaporfin sodium and sodium-pheophorbide a, which can be regarded as photosensitizers for photodynamic therapy,...
Fluorescence spectra and fluorescence lifetime images of talaporfin sodium and sodium-pheophorbide a, which can be regarded as photosensitizers for photodynamic therapy, were measured in normal and cancer cells. The reduction of the fluorescence intensity by photoirradiation was observed for both photosensitizers in both cells, but the quenching rate was much faster in cancer cells than in normal cells. These results are explained in terms of the excessive generation of reactive oxygen species via photoexcitation of these photosensitizers in cancer cells. The fluorescence lifetimes of both photosensitizers in cancer cells are different from those in normal cells, which originates from the different intracellular environments around the photosensitizers between normal and cancer cells.
Topics: Animals; Cell Line, Tumor; Chlorophyll; Photosensitizing Agents; Porphyrins; Rats; Spectrometry, Fluorescence
PubMed: 25993516
DOI: 10.3390/s150511417 -
Radiation Oncology (London, England) Jul 2012Photodynamic therapy (PDT) is a less invasive and effective salvage treatment for local failure after chemoradiotherapy (CRT) for esophageal cancer, however it causes a...
BACKGROUND
Photodynamic therapy (PDT) is a less invasive and effective salvage treatment for local failure after chemoradiotherapy (CRT) for esophageal cancer, however it causes a high rate of skin phototoxicity and requires a long sun shade period. Talaporfin sodium is a rapidly cleared photosensitizer that is expected to have less phototoxicity. This study was undertaken to clarify the optimum laser fluence rate of PDT using talaporfin sodium and a diode laser for patients with local failure after CRT or radiotherapy (RT) for esophageal cancer.
METHODS
This phase I, laser dose escalation study used a fixed dose (40 mg/m²) of intravenous talaporfin sodium administered 4 to 6 hours before irradiation in patients with local failure limited to T2 after CRT or RT (≥ 50 Gy). The primary endpoint was to assess the dose limiting toxicity (DLT) of PDT, and the secondary endpoints were to evaluate the adverse events and toxicity related to PDT. The starting fluence of the 664 nm diode laser was 50 J/cm², with an escalation plan to 75 J/cm² and 100 J/cm².
RESULTS
9 patients with local failure after CRT or RT for ESCC were enrolled and treated in groups of 3 individuals to the third fluence level. No DLT was observed at any fluence level. Phototoxicity was not observed, but one subject had grade 1 fever, three had grade 1 esophageal pain, and 1 had grade 1 dysphagia. Five of 9 patients (55.6%) achieved a complete response after PDT.
CONCLUSIONS
PDT using talaporfin sodium and a diode laser was safe for local failure after RT in patients with esophageal cancer. The recommended fluence for the following phase II study is 100 J/cm².
Topics: Aged; Aged, 80 and over; Chemoradiotherapy; Esophageal Neoplasms; Humans; Lasers, Semiconductor; Male; Middle Aged; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Porphyrins; Salvage Therapy
PubMed: 22824179
DOI: 10.1186/1748-717X-7-113 -
Journal of Clinical Medicine May 2020A phase II study of second-generation photodynamic therapy (PDT) using talaporfin sodium has shown excellent treatment results for esophageal cancer with local failure...
A phase II study of second-generation photodynamic therapy (PDT) using talaporfin sodium has shown excellent treatment results for esophageal cancer with local failure after chemoradiotherapy (CRT) or radiotherapy (RT). However, only a few studies have reported this therapy in clinical practice. This study aimed to confirm the efficacy and safety of salvage PDT using talaporfin sodium for esophageal cancer in various clinical situations. Twelve patients with esophageal cancer with local failure after definitive CRT or RT who underwent PDT using talaporfin sodium were enrolled from April 2016 to January 2020. Overall, 10 patients (83.3%) achieved a local complete response. No skin phototoxicity was observed, but esophageal stricture occurred in five patients (41.7%). Esophageal stricture was improved with endoscopic balloon dilation in all patients, and subsequent analysis found no significant factors causing esophageal stricture after PDT. Two patients with synchronous tumors were successfully rescued by combination therapy with endoscopic submucosal dissection. Two patients with carcinoma in situ of larger than 1/2 circumference were rescued by repeated PDT. The 2-year overall survival was 80.0% (95% confidence interval 0.409-0.946). PDT using talaporfin sodium was an effective and safe salvage treatment for esophageal cancer with local failure after CRT or RT in various clinical situations.
PubMed: 32429571
DOI: 10.3390/jcm9051509 -
Laser Therapy Dec 2019Photodynamic therapy (PDT), a minimally invasive cancer treatment involving the activation of photosensitizer by a specific wavelength of light, is considered to be a...
BACKGROUND
Photodynamic therapy (PDT), a minimally invasive cancer treatment involving the activation of photosensitizer by a specific wavelength of light, is considered to be a promising treatment option for drug-resistant prostate cancer. Hemagglutinating virus of Japan envelope (HVJ-E) has the potential to serve as a highly effective cancer therapy through selective drug delivery and enhancement of the anti-tumor immune response.
OBJECTIVES
To improve therapeutic efficacy and selective accumulation of photosensitizer into tumor cells, we developed a novel photosensitizer, Laserphyrin-HVJ-E (L-HVJ-E), by incorporating talaporfin sodium (Laserphyrin, Meiji Seika Pharma) into HVJ-E.
MATERIALS AND METHODS
The therapeutic effect of PDT with Laserphyrin or L-HVJ-E was evaluated in the human prostate cancer cell line PC-3 . The subcellular localizations of Laserphyrin and L-HVJ-E were observed by confocal microscopy. Apoptosis or necrosis following PDT was detected by annexin V-fluorescein/propidium iodide double staining.
RESULTS
The cytotoxic effect of Laserphyrin- and L-HVJ-E-mediated PDT were determined by evaluating cell survival rate and production of reactive oxygen species. The cytotoxicity of L-HVJ-E-mediated PDT was dependent on drug concentration and light dose. Laserphyrin and L-HVJ-E gradually entered cells as incubation time increased, and both agents tended to be distributed in lysosomes rather than mitochondria. Time and dose dependent increase in ROS production was observed, and induction of both apoptotic and necrotic cell death was confirmed.
CONCLUSIONS
Laserphyrin and L-HVJ-E were distributed mainly in lysosomes and induced cell death by both apoptosis and necrosis. Furthermore, L-HVJ-E-mediated PDT effectively killed cultured PC-3 cells and exerted higher photocytotoxicity than Laserphyrin-mediated PDT.
PubMed: 32255916
DOI: 10.5978/islsm.19-OR-11