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Photodiagnosis and Photodynamic Therapy Mar 2009We aimed to clarify the optimal timing for the fluorescence imaging of brain tumor tissue differentiated from brain edema after the administration of photosensitizers.
OBJECTIVE
We aimed to clarify the optimal timing for the fluorescence imaging of brain tumor tissue differentiated from brain edema after the administration of photosensitizers.
METHODS
We have performed an in vivo study of the kinetics of 5-aminolevulinic acid (5-ALA) in comparison with talaporfin sodium using the rat brain tumor model and rat vasogenic edema model produced by cold injury. The in vivo kinetics of 5-ALA and talaporfin sodium in brain tumor model and the vasogenic edema model was determined by a fluorescence macroscope and a microplate reader.
RESULTS
The in vivo kinetic study of 5-ALA showed mild fluorescence intensity of protoporphyrin IX (PpIX) in brain tumor differentiated from vasogenic edema. The mean lesion-to-normal-brain ratio (L/N ratio) in the group of brain tumor model 2h after the administration of 5-ALA was 7.78+/-4.61, which was significantly higher (P<0.01) than that of the vasogenic edema 2h after the administration of 5-ALA (2.75+/-1.12). In vivo kinetic study of talaporfin sodium showed high fluorescence intensity and retention in brain tumor differentiated from vasogenic edema. The mean L/N ratio of the fluorescence intensity in the group of brain tumor model 12h after the administration of talaporfin sodium was 23.1+/-11.9, which was significantly higher (P<0.01) than that of the vasogenic edema 12h after the administration (8.93+/-8.03).
CONCLUSIONS
The optimization of fluorescence imaging of brain tumors differentiated from brain edema is possible in the case of 5-ALA within 6h, and also possible in the case of talaporfin sodium beyond 12h.
Topics: Aminolevulinic Acid; Animals; Brain; Brain Edema; Brain Neoplasms; Diagnosis, Differential; Image Enhancement; Kinetics; Metabolic Clearance Rate; Microscopy, Fluorescence; Photosensitizing Agents; Porphyrins; Rats; Rats, Wistar
PubMed: 19447368
DOI: 10.1016/j.pdpdt.2009.03.005 -
PloS One 2014Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical...
Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC.
Topics: Animals; Apoptosis; Carcinoma, Squamous Cell; Cell Adhesion; Cell Line, Tumor; Cell Proliferation; DNA Breaks, Double-Stranded; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Fluorescence; Humans; Intracellular Space; Mice; Photochemotherapy; Porphyrins; Reactive Oxygen Species; Reproducibility of Results
PubMed: 25090101
DOI: 10.1371/journal.pone.0103126 -
Cancers Jun 2023Near-infrared photoimmunotherapy (NIR-PIT) is a new phototherapy that utilizes a monoclonal antibody (mAb) against cancer antigens and a phthalocyanine dye, IRDye700DX...
Near-infrared photoimmunotherapy (NIR-PIT) is a new phototherapy that utilizes a monoclonal antibody (mAb) against cancer antigens and a phthalocyanine dye, IRDye700DX (IR700) conjugate (mAb-IR700). Photodynamic therapy (PDT) is a combination therapy that utilizes photoreactive agents and light irradiation as well as NIR-PIT. In the present study, we compared these therapies in vitro. The characterization of cellular binding/uptake specificity and cytotoxicity were examined using two mAb-IR700 forms and a conventional PDT agent, talaporfin sodium, in three cell lines. As designed, mAb-IR700 had high molecular selectivity and visualized target molecule-positive cells at the lowest concentration examined. NIR-PIT induced necrosis and damage-associated molecular patterns (DAMPs), a surrogate maker of immunogenic cell death. In contrast, talaporfin sodium was taken up by cells regardless of cell type, and its uptake was enhanced in a concentration-dependent manner. PDT induced cell death, with the pattern of cell death shifting from apoptosis to necrosis depending on the concentration of the photosensitizer. Induction of DAMPs was observed at the highest concentration, but their sensitivity differed among cell lines. Overall, our data suggest that molecule-specific NIR-PIT may have potential advantages compared with PDT in terms of the efficiency of tumor visualization and induction of DAMPs.
PubMed: 37444510
DOI: 10.3390/cancers15133400 -
The Journal of Toxicological Sciences 2018Photodynamic therapy (PDT) using talaporfin sodium (TS) is tumor cell-selective less invasive therapy for the treatment of malignant glioma. We previously demonstrated...
Photodynamic therapy (PDT) using talaporfin sodium (TS) is tumor cell-selective less invasive therapy for the treatment of malignant glioma. We previously demonstrated that PDT using TS (TS-PDT) treatment exhibits anti-tumor activity against not only glioblastoma cells but also malignant meningioma cells. In general, various stress response proteins have been reported to affect the sensitivity determination for anticancer agents against tumor cells. However, the relationship between the therapeutic effect of TS-PDT and stress response systems in tumor cells is not adequately investigated. In this study, we investigated the gene expression of stress response proteins, including Sod1, Cat1, Gstp1, Gpx1, Nqo1, and Hmox1, in rat malignant meningioma KMY-J cells after treatment of TS-PDT. TS-PDT treatment significantly decreased the cell viability when compared with the no laser irradiation group. In morphological observation, TS at 25.6 µM treatment exhibited a significant cytotoxic effect after 12 hr of laser irradiation to KMY-J cells. After 3 and 6 hr of TS-PDT treatment, mRNA expression of heme oxygenase-1 (HO-1, encoded by Hmox1) was significantly increased by TS-PDT treatment. We also demonstrated that zinc protoporphyrin IX (ZnPPIX), a HO-1 inhibitor, significantly augmented the cytotoxic effect of TS-PDT treatment. These data suggest that HO-1 induction may contribute to a protective response against TS-PDT treatment in the malignant meningioma cells and may attenuate the therapeutic effect for TS-PDT treatment.
Topics: Animals; Antineoplastic Agents; Cell Survival; Drug Synergism; Gene Expression; Heme Oxygenase-1; Meningioma; Photochemotherapy; Photosensitizing Agents; Porphyrins; Protoporphyrins; RNA, Messenger; Rats; Time Factors; Tumor Cells, Cultured
PubMed: 29743446
DOI: 10.2131/jts.43.353 -
ACS Omega Sep 2022Chromophore-assisted light inactivation (CALI) was applied to molecule-targeted photodynamic therapy (PDT). In order to identify organic photosensitizers suitable for...
Chromophore-assisted light inactivation (CALI) was applied to molecule-targeted photodynamic therapy (PDT). In order to identify organic photosensitizers suitable for CALI, the carbonic anhydrase II (CAII) ligand, 4-sulfamoylbenzoic acid , was conjugated with several photosensitizers to produce compounds , whose CALI ability was evaluated by measuring their effect on CAII enzymatic activity. Di-iodinated BODIPY (IBODIPY) exhibited excellent CAII inactivation ability, similar to that of Ru(bpy). The glucose-IBODIPY conjugate () was synthesized as an inactivation of glucose transporter 1 (GLUT1), a protein overexpressed in many cancer cells. Under light irradiation, exhibited concentration-dependent cytotoxicity with half maximal inhibitory concentration (IC) values of 5.49, 11.14, and 8.73 μM, against human cervical carcinoma (HeLa), human lung carcinoma (A549), and human hepatocellular carcinoma (HepG2) cell lines, respectively. The GLUT1 inhibitor phloretin suppressed the cytotoxicity induced by under light irradiation in a concentration-dependent manner. Western blot analysis indicated that GLUT1 was not detected in cell lines treated with 10 μM under light irradiation. Furthermore, reduced the levels of epidermal growth factor receptor tyrosine kinase (EGFR), phospho-ERK (Y204), and GLUT1 without affecting ERK, α-tubulin, and PCNA protein levels, whereas talaporfin sodium, a clinically approved photosensitizer for PDT, nonspecifically reduced intracellular protein levels in HeLa cells, indicating that has a GLUT1-specific inactivation ability and causes light-induced cytotoxicity by modulating the EGFR/MAPK signaling pathway.
PubMed: 36188330
DOI: 10.1021/acsomega.2c05042 -
Photodiagnosis and Photodynamic Therapy Mar 2023Photodynamic therapy (PDT) has been shown to be effective and safe in the treatment of malignant central airway stenosis. However, the laser dose for talaporfin PDT is...
Photodynamic therapy (PDT) has been shown to be effective and safe in the treatment of malignant central airway stenosis. However, the laser dose for talaporfin PDT is unclear. We herein review cases where talaporfin PDT was used to treat malignant central airway stenosis. A total of 17 lesions were treated with talaporfin PDT at laser doses of 50-150 J/cm. Improvement of airway stenosis was observed in all cases except for 1 lesion treated with a dose of 50 J/cm. The results show that talaporfin PDT with 100 J/cm of laser dose is a feasible treatment for malignant central airway stenosis. (This is a secondary publication from the Journal of Japan Society for Laser Surgery and Medicine 2022; 43(1): 9-12.).
Topics: Humans; Photochemotherapy; Photosensitizing Agents; Constriction, Pathologic; Porphyrins; Lasers
PubMed: 36739957
DOI: 10.1016/j.pdpdt.2023.103315 -
Frontiers in Oncology 2022Photodynamic therapy (PDT) targets tumor cell remnants after resection. Here, we evaluated the feasibility of PDT for malignant brain tumors in children and young...
Photodynamic therapy (PDT) targets tumor cell remnants after resection. Here, we evaluated the feasibility of PDT for malignant brain tumors in children and young adolescents. This was a single-center, non-randomized, phase I/II clinical study. The primary endpoints were the safety of treatment with talaporfin sodium (TS) (phase I) and overall survival (OS) after PDT (phase II). The secondary endpoint was progression-free survival (PFS) after PDT. The TS dose was determined by dose escalation from 10 to 20 to 40 mg/m for every three cases starting from the initial enrolled case. Eight patients with a mean age of 170.2 months (129-214 months) at the time of PDT received nine procedures with a mean follow-up duration of 16.8 months (1-42 months) after PDT. Histopathological diagnoses included supratentorial anaplastic ependymoma (n = 2), anaplastic astrocytoma (n = 1), diffuse midline glioma with H3K27M mutation (n = 1), glioblastoma (n = 3), and pediatric high-grade glioma (n = 1). The outcome was survival in five patients and death in three patients. Recurrence occurred in six of the eight patients; the remaining two were recurrence-free after PDT. Therefore, OS and PFS were calculated as 21 and 6 months, respectively. Seizures and fevers, which were likely surgery-related symptoms, were commonly observed. Photosensitive skin rashes or liver dysfunction, which are common adverse effects in adults, were not observed. Our results showed that TS can be used safely in children at doses comparable to those used in adults, as there was no major complication associated with TS administration. However, we cannot make a definitive conclusion about the efficacy of PDT because of the small number of participants. Accumulating cases was difficult because of the rarity of pediatric brain tumors and the difficulty in making a preoperative differential diagnosis, considering the wide range of histopathological findings. Moreover, the psychological stress associated with light-shielding management in pediatric patients was more severe than initially expected. In conclusion, TS at doses comparable to those used in adults may be safe for use in children and young adolescents between the ages of 6 and 20 years. However, further studies are needed to clarify its efficacy.
PubMed: 36505805
DOI: 10.3389/fonc.2022.957267 -
Photodiagnosis and Photodynamic Therapy Sep 2015What is the current status of photodynamic therapy (PDT) with regard to treating malignant brain tumors? Despite several decades of effort, PDT has yet to achieve... (Review)
Review
INTRODUCTION
What is the current status of photodynamic therapy (PDT) with regard to treating malignant brain tumors? Despite several decades of effort, PDT has yet to achieve standard of care.
PURPOSE
The questions we wish to answer are: where are we clinically with PDT, why is it not standard of care, and what is being done in clinical trials to get us there.
METHOD
Rather than a meta-analysis or comprehensive review, our review focuses on who the major research groups are, what their approaches to the problem are, and how their results compare to standard of care. Secondary questions include what the effective depth of light penetration is, and how deep can we expect to kill tumor cells.
CURRENT RESULTS
A measurable degree of necrosis is seen to a depth of about 5mm. Cavitary PDT with hematoporphyrin derivative (HpD) results are encouraging, but need an adequate Phase III trial. Talaporfin with cavitary light application appears promising, although only a small case series has been reported. Foscan for fluorescence guided resection (FGR) plus intraoperative cavitary PDT results were improved over controls, but are poor compared to other groups. 5-Aminolevulinic acid-FGR plus postop cavitary HpD PDT show improvement over controls, but the comparison to standard of care is still poor.
CONCLUSION
Continued research in PDT will determine whether the advances shown will mitigate morbidity and mortality, but certainly the potential for this modality to revolutionize the treatment of brain tumors remains. The various uses for PDT in clinical practice should be pursued.
Topics: Aminolevulinic Acid; Brain Neoplasms; Cell Death; Clinical Trials as Topic; Fluorescence; Hematoporphyrin Derivative; Humans; Infratentorial Neoplasms; Mesoporphyrins; Nitric Oxide; Photochemotherapy; Photosensitizing Agents; Porphyrins; Signal Transduction; Surgery, Computer-Assisted
PubMed: 25960361
DOI: 10.1016/j.pdpdt.2015.04.009 -
Internal Medicine (Tokyo, Japan) Apr 2024Introduction Photodynamic therapy (PDT) is a salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Salvage PDT is the treatment available...
Introduction Photodynamic therapy (PDT) is a salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Salvage PDT is the treatment available for vulnerable patients with various comorbidities at risk of salvage esophagectomy. This study assessed the impact of the Charlson comorbidity index (CCI) on the outcomes of salvage PDT using talaporfin sodium (TS) for esophageal cancer. Metohds Consecutive patients with esophageal cancer who underwent salvage TS-PDT from 2016 to 2022 were included in this retrospective study. We investigated the local complete response (L-CR), progression-free survival (PFS) and overall survival (OS) and evaluated the relationship between the CCI and therapeutic efficacy. Results In total, 25 patients were enrolled in this study. Overall, 12 patients (48%) achieved an L-CR, and the 2-year PFS and OS rates were 24.9% and 59.4%, respectively. In a multivariate analysis, a CCI ≥1 (p=0.041) and deeper invasion (p=0.048) were found to be significant independent risk factors for not achieving an L-CR. To evaluate the efficacy associated with comorbidities, we divided the patients into the CCI=0 group (n=11) and the CCI ≥1 group (n=14). The rate of an L-CR (p=0.035) and the 2-year PFS (p=0.029) and OS (p=0.018) rates in the CCI ≥1 group were significantly lower than those in the CCI=0 group. Conclusion This study found that the CCI was negatively associated with the efficacy of salvage TS-PDT for esophageal cancer.
Topics: Humans; Photosensitizing Agents; Photochemotherapy; Salvage Therapy; Retrospective Studies; Esophageal Neoplasms; Comorbidity; Treatment Outcome; Porphyrins
PubMed: 37558484
DOI: 10.2169/internalmedicine.1907-23 -
The Keio Journal of Medicine Sep 2009Mono-L-aspartyl chlorin e6 (Talaporfin sodium) is a novel photosensitizer, and is currently being used in photodynamic therapy for various malignant tumors in...
BACKGROUND
Mono-L-aspartyl chlorin e6 (Talaporfin sodium) is a novel photosensitizer, and is currently being used in photodynamic therapy for various malignant tumors in combination with irradiation with a 664 nm laser. An interesting characteristic of Talaporfin sodium is that the skin photosensitivity after injection of this agent disappears faster than any other existing photosensitizers. This study examined the vascular events that occurred postirradiation in the chicken comb as a capillary malformation model after photosensitization with Talaporfin sodium.
MATERIALS AND METHODS
A single intravenous bolus injections of Talaporfin sodium was administered to the chickens, and a 1 cm diameter area of the comb of each animal was irradiated with a 664 nm visible red laser. The gross changes in the chicken combs were recorded for 7-14 days after photodynamic therapy. For the histological examination, HE, PTAH and Azan stained sections were analyzed.
RESULTS
All treated chicken combs had blanched after photodynamic therapy. Microscopy demonstrated an absence of erythrocytes and the vessel lumina were obliterated, leaving the normal overlying epidermis completely intact. Concomitantly with selective destruction of the capillaries in the target area, moderate invasion of inflammatory cells and a slight increase in the stroma were observed.
CONCLUSIONS
In the chicken comb model, photodynamic therapy with Talaporfin sodium effectively achieved selective destruction of the microvasculature while leaving the epidermis intact. Our results strongly suggest that photodynamic therapy with Talaporfin sodium could be a feasible method to treat dermal hypervascular lesions.
Topics: Animals; Capillaries; Chickens; Chlorophyllides; Comb and Wattles; Erythrocytes; Inflammation; Male; Photochemotherapy; Photosensitizing Agents; Porphyrins; Port-Wine Stain; Radiation-Sensitizing Agents; Skin; Skin Diseases
PubMed: 19826211
DOI: 10.2302/kjm.58.176