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Acta Dermato-venereologica Apr 2024Simulated daylight photodynamic therapy is a relatively new and potentially less painful alternative to conventional red light photodynamic therapy for actinic...
Exploring Patient Pain Experiences during and after Conventional Red Light and Simulated Daylight Photodynamic Therapy for Actinic Keratosis: A Qualitative Interview Study.
Simulated daylight photodynamic therapy is a relatively new and potentially less painful alternative to conventional red light photodynamic therapy for actinic keratosis. Qualitative research exploring patient experiences of pain and skin reactions during these treatments is scarce. To address this, semi-structured interviews were conducted of 10 patients aged 60-81 years with symmetrically distributed actinic keratoses 4 weeks after split-face treatment with conventional red light photodynamic therapy and simulated daylight photodynamic therapy. The participants were recruited from an ongoing clinical randomized trial. Interviews (median length 35 min) were conducted between June 2022 and January 2023, audio-recorded, transcribed verbatim, and analysed qualitatively using content analysis, as described by Graneheim and Lundman. Participants reported that conventional red light photodynamic therapy was very painful during illumination and transiently painful in the post-treatment period, while simulated daylight photodynamic therapy was almost painless during illumination and led to minor post-treatment pain. Also, skin reactions were more intense and longer-lasting with conventional red light photodynamic therapy than with simulated daylight photodynamic therapy. Most participants expressed a treatment preference for simulated daylight photodynamic therapy but had reservations about its unestablished long-term effectiveness. This study underscores the considerable pain associated with conventional red light photodynamic therapy, and the pivotal importance of shared decision-making when selecting the most appropriate treatment.
Topics: Humans; Aminolevulinic Acid; Keratosis, Actinic; Pain; Photochemotherapy; Photosensitizing Agents; Red Light; Treatment Outcome
PubMed: 38596905
DOI: 10.2340/actadv.v104.19459 -
Photodiagnosis and Photodynamic Therapy Apr 2024Vascular-targeted photodynamic therapy (V-PDT) is a clinically approved therapeutic approach for treating vascular-related diseases, such as port-wine stains (PWS). For...
SIGNIFICANCE
Vascular-targeted photodynamic therapy (V-PDT) is a clinically approved therapeutic approach for treating vascular-related diseases, such as port-wine stains (PWS). For accurate treatment, varying light irradiance is required for different lesions due to the irregularity of vascular size, shape and degree of disease, which commonly alters during different stages of V-PDT. This makes quantitative analysis of the treatment efficiency urgently needed.
APPROACH
Lesion images pre- and post- V-PDT treatment of patients with PWS were used to construct a quantitative method to evaluate the differences among lesions. Image analysis techniques were applied to evaluate the V-PDT efficiency for PWS by determining the Euclidean distances and two-dimensional correlation coefficients.
RESULTS
According to the image analysis, V-PDT with good treatment efficiency resulted in a larger Euclidean distance and a smaller correlation coefficient compared with the case having lower V-PDT efficiency.
CONCLUSIONS
A new method to quantify the Euclidean distances and correlation coefficients has been proposed, which is promising for the quantitative analysis of V-PDT efficiency for PWS.
Topics: Port-Wine Stain; Photochemotherapy; Humans; Photosensitizing Agents; Female; Male; Adult; Aminolevulinic Acid; Child; Adolescent
PubMed: 38588873
DOI: 10.1016/j.pdpdt.2024.104081 -
Photodiagnosis and Photodynamic Therapy Apr 2024Photodynamic therapy (PDT) can be targeted toward different subcellular localizations, and it is proposed that different subcellular targets vary in their sensitivity to...
SIGNIFICANCE
Photodynamic therapy (PDT) can be targeted toward different subcellular localizations, and it is proposed that different subcellular targets vary in their sensitivity to photobiological damage. Since singlet oxygen (O) has a very short lifetime with a limited diffusion length in cellular environments, measurement of cumulative O luminescence is the most direct approach to compare the PDT sensitivity of mitochondria and plasma membrane.
APPROACH
PDT-generated near-infrared O luminescence at 1270 nm was measured together with cell viability for 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) and exogenous PpIX, at different incubation times. Confocal fluorescence microscopy indicated that ALA-induced PpIX (2 h) localized in the mitochondria, whereas exogenous PpIX (1 h) mainly localized to the plasma membrane. Cell viability was determined at several time points during PDT treatments using colony-forming assays, and the surviving fraction correlated well with cumulative O luminescence counts from PpIX in mitochondria and plasmas membrane, respectively.
RESULTS
The mitochondria are more sensitive than the plasma membrane by a factor of 1.7.
CONCLUSIONS
Direct O luminescence dosimetry's potential value for comparing the PDT sensitivity of different subcellular organelles was demonstrated. This could be useful for developing subcellular targeted novel photosensitizers to enhance PDT efficiency.
Topics: Protoporphyrins; Singlet Oxygen; Photosensitizing Agents; Photochemotherapy; Mitochondria; Cell Survival; Cell Membrane; Aminolevulinic Acid; Humans
PubMed: 38583747
DOI: 10.1016/j.pdpdt.2024.104080 -
Journal of Inorganic Biochemistry Jul 2024Trinuclear ruthenium(II) polypyridyl complexes anchored to benzimidazole-triazine / trisamine scaffolds were investigated as photosensitizers for photodynamic therapy....
Trinuclear ruthenium(II) polypyridyl complexes anchored to benzimidazole-triazine / trisamine scaffolds were investigated as photosensitizers for photodynamic therapy. The trinuclear complexes were noted to produce a significant amount of singlet oxygen in both DMF and aqueous media, are photostable and show appreciable emission quantum yields (ɸ). In our experimental setting, despite the moderate phototoxic activity in the HeLa cervical cancer cell line, the phototoxic indices (PI) of the trinuclear complexes are superior relative to the PIs of a clinically approved photosensitizer, Photofrin®, and the pro-drug 5-aminolevulinic acid (PI: >7 relative to PI: >1 and PI: 4.4 for 5-aminolevulinic acid and Photofrin®, respectively). Furthermore, the ruthenium complexes were noted to show appreciable long-term cytotoxicity upon light irradiation in HeLa cells in a concentration-dependent manner. Consequently, this long-term activity of the ruthenium(II) polypyridyl complexes embodies their ability to reduce the probability of the recurrence of cervical cancer. Taken together, this presents a strong motivation for the development of polymetallic complexes as anticancer agents.
Topics: Humans; Photosensitizing Agents; HeLa Cells; Uterine Cervical Neoplasms; Ruthenium; Female; Coordination Complexes; Photochemotherapy; Antineoplastic Agents; Pyridines; Singlet Oxygen
PubMed: 38581803
DOI: 10.1016/j.jinorgbio.2024.112545 -
Heliyon Apr 2024Gadolinium-enhancing necrosis in glioblastoma multiforme (GBM), as an occasionally occurring false positive in contrast enhancement (CE) imaging, leads to trouble for...
PURPOSE
Gadolinium-enhancing necrosis in glioblastoma multiforme (GBM), as an occasionally occurring false positive in contrast enhancement (CE) imaging, leads to trouble for segmentation of GBM and treatment. Therefore, the investigation of complementary detection way to identify the metabolically active volume of the tumor with high reliability is very worth to be addressed. Here, we reported on a case of GBM with gadolinium-enhancing necrosis in an experimental CE imaging study in mice and evaluated the discrimination of the necrosis and metabolically active parts of the GBM using conventional and state-of-the-art susceptibility-based MRI.
METHODS
In this study, following 5-aminolevulinic acid (ALA) and iron supplements (FAC, 6 h after ALA, intra-tumoral injection) to animal, T*-W imaging and quantitative susceptibility mapping (QSM) were performed, and compared with CE imaging.
RESULTS
The signal intensity (SI) of the active and necrosis areas of the case in the CE image demonstrated no significant difference while the SI on the T*-W images and susceptibility value in QSM changed 24 and 150%, respectively.
CONCLUSION
The preclinical case report provides valuable insights into the potential of susceptibility-based MRI using ALA + FAC to apply as a robust discriminator between necrotic and viable tumors.
PubMed: 38571593
DOI: 10.1016/j.heliyon.2024.e28355 -
Acta Neurochirurgica Apr 2024Glioblastoma is the most common primary malignant brain tumor. Despite advances in multimodal concepts over the last decades, prognosis remains poor. Treatment of... (Review)
Review
Glioblastoma is the most common primary malignant brain tumor. Despite advances in multimodal concepts over the last decades, prognosis remains poor. Treatment of patients with glioblastoma remains a considerable challenge due to the infiltrative nature of the tumor, rapid growth rates, and tumor heterogeneity. Standard therapy consists of maximally safe microsurgical resection followed by adjuvant radio- and chemotherapy with temozolomide. In recent years, local therapies have been extensively investigated in experimental as well as translational levels. External stimuli-responsive therapies such as Photodynamic Therapy (PDT), Sonodynamic Therapy (SDT) and Radiodynamic Therapy (RDT) can induce cell death mechanisms via generation of reactive oxygen species (ROS) after administration of five-aminolevulinic acid (5-ALA), which induces the formation of sensitizing porphyrins within tumor tissue. Preliminary data from clinical trials are available. The aim of this review is to summarize the status of such therapeutic approaches as an adjunct to current standard therapy in glioblastoma.
Topics: Humans; Glioblastoma; Aminolevulinic Acid; Fluorescence; Temozolomide; Reactive Oxygen Species
PubMed: 38563988
DOI: 10.1007/s00701-024-06049-3 -
Journal of Neurosurgery Mar 2024The highly infiltrative growth of glioblastoma (GBM) makes distinction between the tumor and normal brain tissue challenging. Therefore, fluorescence-guided surgery is...
OBJECTIVE
The highly infiltrative growth of glioblastoma (GBM) makes distinction between the tumor and normal brain tissue challenging. Therefore, fluorescence-guided surgery is often used to improve visual identification of radiological tumor margins. The aim of this study was to evaluate the ability of recently developed molecularly targeted near-infrared (NIR) protease-activated probes to visualize GBM tissue and to compare the most promising candidate with the gold standard, 5-aminolevulinic acid (5-ALA).
METHODS
Single-substrate probes 6QC-ICG and 6QC-Cy5 (cysteine cathepsin cleavable), double-substrate probes AG2-FNIR and AG2-Cy5 (cysteine cathepsin and caspase 3 cleavable), and 5-ALA were administered intravenously to mice with orthotopic tumors. Activation of the probes was also evaluated in cell cultures in vitro and in biopsy material from patients with GBM ex vivo. The tumor to normal brain tissue fluorescence ratio (TNR) was quantified in brain sections using preclinical and clinical visualization platforms, and in tissue homogenates and cell suspensions using spectrofluorimetry. Subcellular localization of the fluorophores was visualized by confocal microscopy.
RESULTS
In vitro, the single-substrate probe 6QC-ICG was cleaved in glioma cells and macrophages, and the resulting fluorophore accumulated intracellularly. In experimental GBMs, both single- and double-substrate probes visualized tumor tissue, while in healthy brain tissue the signal was minimal. TNR was highest for 6QC-ICG and AG2-FNIR, but the signal intensity was higher for 6QC-ICG. Using xenograft and syngeneic mouse models, as well as human GBM biopsy material ex vivo, the authors confirmed the ability of 6QC-ICG to specifically visualize the glioma tissue using preclinical and clinical visualization platforms. Finally, a comparison with 5-ALA in animals coadministered with both compounds revealed a higher TNR for 6QC-ICG in experimental GBMs.
CONCLUSIONS
The cysteine cathepsin-cleavable probe 6QC-ICG is activated by glioma cells and tumor-associated macrophages, leading to a high contrast between tumor and nontumorous brain tissue that is superior to that of the current standard, 5-ALA. In addition to a well-defined mechanism of action, protease-activated probes that use NIR fluorophores (e.g., indocyanine green) have the advantage of low absorption and scattering of the NIR light and lower tissue autofluorescence. These results suggest that 6QC-ICG has the potential to become the targeted agent in intraoperative detection of GBM tissue using fluorescence imaging.
PubMed: 38552239
DOI: 10.3171/2024.1.JNS231137 -
Annals of Agricultural and... Mar 2024Photodynamic therapy (PDT) is a therapeutic option for low-risk basal cell carcinoma (BCC). The aim of the study was to assess the efficacy of topical PDT in the...
INTRODUCTION AND OBJECTIVE
Photodynamic therapy (PDT) is a therapeutic option for low-risk basal cell carcinoma (BCC). The aim of the study was to assess the efficacy of topical PDT in the treatment of superficial BCC (sBCC) using two different photosensitizers: aminolevulinic acid hydrochloride (ALA-HCl) in a gel formulation with a lipid nanoemulsion (ALA-HCl in gel) and ALA methyl ester hydrochloride (MAL-HCl) in a cream formulation (MAL-HCl in cream).
MATERIAL AND METHODS
21 patients were treated twice with a one week interval between treatments. The formulations were applied onto lesions: 10 patients were treated with MAL-HCl in cream, and 11 with ALA-HCl in gel. After three hours of incubation and removing the preparations, fluorescence was assessed. The skin areas were then irradiated with red light 630 ± 5 nm.
RESULTS
At the follow-up visit 12 weeks after the second treatment, complete clinical remission was found in 82% after ALA-HCl in gel and in 80% after MAL-HCl in cream. An excellent cosmetic result was found in 96% of patients after MALHCl in cream and in 100% after ALA-HCl in gel. Faster skin healing and less post-inflammatory hyperpigmentation during follow-up visits was observed after treatment with ALA-HCl in gel.
CONCLUSIONS
Both formulations - ALA-HCl in gel and MAL-HCl in cream - were highly effective photosensitisers for PDT. The advantage of ALA-HCl in a gel formulation with a lipid nanoemulsion was faster skin healing, resulting in better cosmetic results.
Topics: Humans; Skin Neoplasms; Photochemotherapy; Treatment Outcome; Carcinoma, Basal Cell; Aminolevulinic Acid; Pathologic Complete Response; Lipids
PubMed: 38549482
DOI: 10.26444/aaem/183059 -
Photodiagnosis and Photodynamic Therapy Apr 2024Herein we describe initial results in a porcine model of a fully implantable device designed to allow closed, repetitive photodynamic treatment of glioblastoma (GBM).
OBJECTIVE
Herein we describe initial results in a porcine model of a fully implantable device designed to allow closed, repetitive photodynamic treatment of glioblastoma (GBM).
METHODS
This implant, Globus Lucidus, is a transparent quartz glass sphere with light-emitting diodes releasing wavelengths of 630 nm (19.5 mW/cm), 405 nm (5.0 mW/cm) or 275 nm (0.9 mW/cm). 5-aminolevulinic acid was the photosensitizing prodrug chosen for use with Globus Lucidus, hence the implants illuminated at 630 nm or 405 nm. An additional 275 nm wavelength-emittance was included to explore the effects of photochemical therapy (PCT) by ultraviolet (UV) light. Twenty healthy domestic pigs underwent right-frontal craniotomies. The Globus Lucidus device was inserted into a surgically created right-frontal lobe cavity. After postoperative recovery, irradiation for up to 30 min daily for up to 14 d, or continuous irradiation for up to 14.6 h was conducted.
RESULTS
Surgery, implants, and repeated irradiations using the different wavelengths were generally well tolerated. Social behavior, wound healing, body weight, and temperature remained unaffected. Histopathological analyses revealed consistent leukocyte infiltration around the intracerebral implant sites with no significant differences between experimental and control groups.
CONCLUSION
This Globus Lucidus porcine study prepares the groundwork for adjuvant, long-term, repeated PDT of the GBM infiltration zone. This is the first report of a fully implantable PDT/PCT device for the potential treatment of GBM. A preclinical effectivity study of Globus Lucidus PDT/PCT is warranted and in advanced stages of planning.
Topics: Animals; Glioblastoma; Photochemotherapy; Swine; Photosensitizing Agents; Aminolevulinic Acid; Brain Neoplasms; Female
PubMed: 38548041
DOI: 10.1016/j.pdpdt.2024.104059 -
International Journal of Molecular... Mar 2024Bladder cancer (BCa) research relying on Omics approaches has increased over the last few decades, improving the understanding of BCa pathology and contributing to a... (Review)
Review
Bladder cancer (BCa) research relying on Omics approaches has increased over the last few decades, improving the understanding of BCa pathology and contributing to a better molecular classification of BCa subtypes. To gain further insight into the molecular profile underlying the development of BCa, a systematic literature search was performed in PubMed until November 2023, following the PRISMA guidelines. This search enabled the identification of 25 experimental studies using mass spectrometry or nuclear magnetic resonance-based approaches to characterize the metabolite signature associated with BCa. A total of 1562 metabolites were identified to be altered by BCa in different types of samples. Urine samples displayed a higher likelihood of containing metabolites that are also present in bladder tumor tissue and cell line cultures. The data from these comparisons suggest that increased concentrations of L-isoleucine, L-carnitine, oleamide, palmitamide, arachidonic acid and glycoursodeoxycholic acid and decreased content of deoxycytidine, 5-aminolevulinic acid and pantothenic acid should be considered components of a BCa metabolome signature. Overall, molecular profiling of biological samples by metabolomics is a promising approach to identifying potential biomarkers for early diagnosis of different BCa subtypes. However, future studies are needed to understand its biological significance in the context of BCa and to validate its clinical application.
Topics: Humans; Biomarkers, Tumor; Urinary Bladder Neoplasms; Urinary Bladder; Metabolomics; Metabolome
PubMed: 38542319
DOI: 10.3390/ijms25063347