Devices and Methods for Dosimetry of Personalized Photodynamic Therapy of Tumors: A Review on Recent Trends.

Significance: Despite the widespread use of photodynamic therapy in clinical practice, there is a lack of personalized methods for assessing the sufficiency of photodynamic exposure on tumors, depending on tissue parameters that change during light irradiation. This can lead to different treatment results. Aim: The objective of this article was to conduct a comprehensive review of devices and methods employed for the implicit dosimetric monitoring of personalized photodynamic therapy for tumors. Methods: The review included 88 peer-reviewed research articles published between January 2010 and April 2024 that employed implicit monitoring methods, such as fluorescence imaging and diffuse reflectance spectroscopy. Additionally, it encompassed computer modeling methods that are most often and successfully used in preclinical and clinical practice to predict treatment outcomes. The Internet search engine Google Scholar and the Scopus database were used to search the literature for relevant articles. Results: The review analyzed and compared the results of 88 peer-reviewed research articles presenting various methods of implicit dosimetry during photodynamic therapy. The most prominent wavelengths for PDT are in the visible and near-infrared spectral range such as 405, 630, 660, and 690 nm. Conclusions: The problem of developing an accurate, reliable, and easily implemented dosimetry method for photodynamic therapy remains a current problem, since determining the effective light dose for a specific tumor is a decisive factor in achieving a positive treatment outcome.

Оn the aggregation of polycationic photosensitizer upon binding to Gram-negative bacteria.

Polycationic photosensitizers (PS) are not susceptible to aggregation in solutions, but their high local concentrations in Gram-negative bacteria can be sufficient for aggregation and reduced effectiveness of antibacterial photodynamic treatment. By measuring fluorescence spectra and kinetics we were able to evaluate the degree of aggregation of polycationic PS ZnPcChol8in Gram-negative bacteria E.coliK12 TG1. Binding of ZnPcChol8toE.coliK12 TG1 leads to an appearance of groups of molecules with shorter PS fluorescence lifetime, a decrease in fluorescence intensity and a shift in the fluorescence spectral maximum. However, we evaluated that about 88% of the fluorescing PS molecules in the bacteria were in an unaggregated state, which indicates only a small reduction in the generation of reactive oxygen species.

Tumor fluorescence and oxygenation monitoring during photodynamic therapy with chlorin e6 photosensitizer.

BACKGROUND: The study is aimed at developing a method for monitoring photodynamic therapy (PDT) of a tumor using chlorin-type photosensitizers (PSs). Lack of monitoring of chlorin e6 (Cе6) photobleaching, hemoglobin oxygenation and blood flow during light exposure can limit the PDT effectiveness. MATERIALS AND METHODS: Phototheranostics includes spectral-fluorescence diagnostics of Ce6 distribution in the NIR range and PDT with simultaneous assessment of hemoglobin oxygenation and tumor blood flow. Fluorescence diagnostics and PDT were performed using the single laser λexc=660 ± 5 nm. RESULTS: Combined spectroscopic PDT monitoring method allowed simultaneous estimation of Ce6 photobleaching, hemoglobin oxygenation and tumor vascular thrombosis during PDT without interrupting the therapeutic light exposure. CONCLUSION: The developed method of tumor phototheranostics using chlorin-type PSs may make it possible to personalize the duration of therapeutic light exposure during PDT.

Evaluation of tissue blood supply during esophagectomy using fluorescent diagnostics and diffuse scattering spectroscopy in visible region.

BACKGROUND: The success of the surgical treatment of a tumor or obstruction of the esophagus with subsequent anastomosis application depends on the level of blood supply to the stitched tissues. Intraoperative assessment of blood flow is widely used in medicine and can be used as a diagnostic method that affects the outcome of surgery and reduces the frequency of postoperative complications for the patient. METHODS: In this work, the assessment of blood supply during esophageal resection operations was carried out using two techniques sequentially: fluorescent diagnostics with indocyanine green and measurement of hemoglobin oxygen saturation by diffuse scattering spectroscopy in the visible wavelength range. The first method was used to assess the integrity of the vascular network structure in the area of anastomosis and blood flow through the sutured tissues, the second one - for local assessment of hemoglobin oxygen saturation in the investigated area. RESULTS: Conducted clinical study involved the participation of nine patients with malignant neoplasms (six cases) or esophageal obstruction (three cases). The presence of postoperative complications was compared with the measurement results. Anastomosis failure was observed in only one patient. According to the results of the study, with the use of the investigated method of assessing blood supply, there is a tendency towards a decrease in the frequency of anastomosis leaks (11.1 % compared with 21.4 %). CONCLUSIONS: Therefore, fluorescent diagnostics with indocyanine green and measurement of hemoglobin oxygen saturation using diffuse scattering spectroscopy were affirmed as methods that allow increasing the safety of surgical procedures by assessing the risk of postoperative complications, including anastomosis failures.

Photodynamic inactivation of bacteria: Why it is not enough to excite a photosensitizer.

BACKGROUND: The development of multidrug resistance (MDR) in infectious agents is one of the most serious global problems facing humanity. Antimicrobial photodynamic therapy (APDT) shows encouraging results in the fight against MDR pathogens, including those in biofilms. METHODS: Photosensitizers (PS), monocationic methylene blue, polycationic and polyanionic derivatives of phthalocyanines, electroneutral and polycationic derivatives of bacteriochlorin were used to study photodynamic inactivation of Gram-positive and Gram-negative planktonic bacteria and biofilms under LED irradiation. Zeta potential measurements, confocal fluorescence imaging, and coarse-grained modeling were used to evaluate the interactions of PS with bacteria. PS aggregation and photobleaching were studied using absorption and fluorescence spectroscopy. RESULTS: The main approaches to ensure high efficiency of bacteria photosensitization are analyzed. CONCLUSIONS: PS must maintain a delicate balance between binding to exocellular and external structures of bacterial cells and penetration through the cell wall so as not to get stuck on the way to photooxidation-sensitive structures of the bacterial cell.

Methylene blue in anticancer photodynamic therapy: systematic review of preclinical studies.

Background: Methylene blue has a long history of clinical application. Thanks to phenothiazine chromophore, it has potential in photodynamic anticancer therapy. In spite of the growing body of literature that has evaluated the action of this dye on different types of cancer, the systematic understanding of this problem is still lacking. Therefore, this systematic review was performed to study the efficacy of methylene blue in photodynamic anticancer therapy. Methods: This systematic review was carried out in accordance with the PRISMA guidelines, and the study protocol was registered in PROSPERO (CRD42022368738). Articles for the systematic review were identified through the PubMed database. SYRCLE's risk of bias tool was used to assess the studies. The results of systematic analysis are presented as narrative synthesis. Results: Ten studies met the inclusion criteria and these full texts were reviewed. In the selected articles, the dosage of dye infusion ranged from 0.04 to 24.12 mg/kg. The effectiveness of photodynamic therapy with methylene blue against different types of cancer was confirmed by a decrease in tumor sizes in seven articles. Conclusion: The results of the systematic review support the suggestions that photodynamic therapy with methylene blue helps against different types of cancer, including colorectal tumor, carcinoma, and melanoma. In cases of nanopharmaceutics use, a considerable increase of anticancer therapy effectiveness was observed. The further research into methylene blue in photodynamic anticancer therapy is needed. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=368738), identifier (CRD42022368738).

Optical Differentiation of Brain Tumors Based on Raman Spectroscopy and Cluster Analysis Methods.

In the present study, various combinations of dimensionality reduction methods with data clustering methods for the analysis of biopsy samples of intracranial tumors were investigated. Fresh biopsies of intracranial tumors were studied in the Laboratory of Neurosurgical Anatomy and Preservation of Biological Materials of N.N. Burdenko Neurosurgery Medical Center no later than 4 h after surgery. The spectra of Protoporphyrin IX (Pp IX) fluorescence, diffuse reflectance (DR) and Raman scattering (RS) of biopsy samples were recorded. Diffuse reflectance studies were carried out using a white light source in the visible region. Raman scattering spectra were obtained using a 785 nm laser. Patients diagnosed with meningioma, glioblastoma, oligodendroglioma, and astrocytoma were studied. We used the cluster analysis method to detect natural clusters in the data sample presented in the feature space formed based on the spectrum analysis. For data analysis, four clustering algorithms with eight dimensionality reduction algorithms were considered.

Photodynamic therapy of lung cancer with photosensitizers based on polycationic derivatives of synthetic bacteriochlorin (experimental study).

BACKGROUND: One of the tasks of anticancer photodynamic therapy is increasing the efficacy of treatment of cancer nodes with large (clinically relevant) sizes using near-infrared photosensitizers (PS). METHODS: The anticancer efficacy and mechanisms of the photodynamic action of PS based on polycationic derivatives of synthetic bacteriochlorin against Lewis lung carcinoma were studied in vitro and in vivo. RESULTS: It was found that studied PS have high phototoxicity against Lewis lung carcinoma cells: the IC50 values were about 0.8 µM for tetracationic PS and 0.5 µM for octacationic PS. In vivo studies have shown that these PS provide effective inhibition of the tumor growth with an increase in the lifespan of mice in the group by more than 130%, and more than 50% survival of mice in the group. CONCLUSIONS: Photosensitizers based on polycationic derivatives of synthetic bacteriochlorin have high photodynamic efficacy caused by the induction of necrosis and apoptosis of cancer cells, including cancer stem cells, and a sharp decrease of mitotic and proliferative activity. Studied polycationic photosensitizers are much more effective at destroying cancer stem cells and newly formed cancer vessels in comparison with anionic photosensitizers, and ensure the cessation of tumor blood flow without hemorrhages and thrombosis.

Near-infrared phototheranostics of tumors with protoporphyrin IX and chlorin e6 photosensitizers.

BACKGROUND: The study aims to develop a method for phototheranostics of tumors in the near-infrared (NIR) range using protoporphyrin IX (PpIX) and chlorin e6 (Ce6) photosensitizers (PSs) MATERIALS AND METHODS: Phototheranostics includes spectral fluorescence diagnostics of PS distribution and photodynamic therapy (PDT) using a single laser in the red spectral range. PpIX and Ce6 fluorescence were registered in the NIR range. PpIX and Ce6 photobleaching was determined during PDT by the change in PS fluorescence. NIR phototheranostics with PpIX and Ce6 were performed on optical phantoms and tumors of patients with oral leukoplakia and basal cell carcinoma. RESULTS: NIR spectral fluorescence diagnostics of optical phantoms with PpIX or Ce6 is possible when fluorescence is excited by 635 or 660 nm lasers. Fluorescence intensity of PpIX and Ce6 was measured in the range of 725-780 nm. The highest values of signal-to-noise in the case of phantoms with PpIX were observed at λexc=635 nm, and for phantoms with Ce6 at λexc=660 nm. NIR phototheranostics provides the detection of tumor tissues with PpIX or Ce6 accumulation. The PSs photobleaching in the tumor during PDT occurs according to a bi-exponential law. CONCLUSION: Phototheranostics of tumors containing PpIX or Ce6 allows fluorescent monitoring of PS distribution in the NIR range and measuring PSs photobleaching during light exposure that provides personalization of the photodynamic exposure duration to deeper tumors. Using a single laser for fluorescence diagnostics and PDT reduces patient treatment time.

Optical spectral diagnostics of the oxygenation level in periodontal tissues and photodynamic therapy using methylene blue in children with cerebral palsy.

Dental diseases occur in children with cerebral palsy three times higher than in healthy children. Low values of the unstimulated salivation rate (<0.3 ml per minute), pH and buffer capacity, changes in enzyme activity and sialic acid concentration, as well as increased saliva osmolarity and total protein concentration, which indicates impaired hydration, are the factors in the development of a gingiva disease in case of cerebral palsy. This leads to increased bacterial agglutination and the formation of acquired pellicle and biofilm, leading to the formation of dental plaque. There is a tendency toward an increase in the concentration of hemoglobin and a decrease in the degree of hemoglobin oxygenation, as well as an increase in the generation of reactive oxygen and nitrogen species. Photodynamic therapy (PDT) with the use of photosensitizer methylene blue improves blood circulation and the degree of oxygenation in periodontal tissues, as well as eliminates a bacterial biofilm. Analysis of back diffuse reflection spectra makes it possible to conduct non-invasive monitoring determine tissue areas with a low level of hemoglobin oxygenation for precision photodynamic exposure. Aim: To improve the effectiveness of phototheranostics methods using, namely PDT with simultaneous optical-spectral control, for the treatment of gingivitis in children with complex dental and somatic status (cerebral palsy). Methods: The study involved 15 children (6-18 y.o.) with various forms of cerebral palsy, in particular, spastic diplegia and atonic-astatic form and with gingivitis. The degree of hemoglobin oxygenation was measured in tissues before PDT and on the 12th day. PDT was performed using laser radiation (λ = 660 nm) with a power density of 150 mW/cm2 with a five-minute application of 0.01% MB. The total light dose was 45 ± 15 J/cm2. For statistical evaluation of the results, a paired Student's t-test was used. Results: The paper presents the results of phototheranostics using methylene blue in children with cerebral palsy. An increase in the level of hemoglobin oxygenation from 50 to 67% (p < 0.001) and a decrease in blood volume in the microcirculatory bed of periodontal tissues were shown. Conclusion: Photodynamic therapy methods with application of methylene blue make it possible to assess the state of the gingival mucosa tissue diseases objectively in real time, and to provide effective targeted therapy for gingivitis in children with cerebral palsy. There is a prospect that they can become widely used clinical methods.

New Conjugates Based on AIS/ZnS Quantum Dots and Aluminum Phthalocyanine Photosensitizer: Synthesis, Properties and Some Perspectives.

Today, fluorescent diagnostics and photodynamic therapy are promising methods for diagnosing and treating oncological diseases. The development of new photosensitizers (PS) is one of the most important tasks to improve the efficiency of both laser-induced diagnostics and therapy. In our study, we conjugated PS with AIS/ZnS triple quantum dots (QDs) to obtain non-aggregated complexes. It was shown that the conjugation of PS with QDs does not change the PS fluorescence lifetime, which is a marker of the preservation of PS photophysical properties. In particular, efficient resonant Förster energy transfer (FRET), from QDs to PS molecules in the conjugate, increases the PS luminescence response. The FRET from QD to PS molecules with different ratios of donor and acceptors are shown. It has been demonstrated that the average efficiency of FRET depends on the ratio of PS and QD and reaches a maximum value of 80% at a ratio of 6 PS molecules per 1 QD molecule. Thus, these studies could help to contribute to the development of new complexes based on QD and PS to improve the efficiency of phototheranostics.

Differentiation of glioblastoma tissues using spontaneous Raman scattering with dimensionality reduction and data classification.

The neurosurgery of intracranial tumors is often complicated by the difficulty of distinguishing tumor center, infiltration area, and normal tissue. The current standard for intraoperative navigation is fluorescent diagnostics with a fluorescent agent. This approach can be further enhanced by measuring the Raman spectrum of the tissue, which would provide additional information on its composition even in the absence of fluorescence. However, for the Raman spectra to be immediately helpful for a neurosurgeon, they must be additionally processed. In this work, we analyzed the Raman spectra of human brain glioblastoma multiforme tissue samples obtained during the surgery and investigated several approaches to dimensionality reduction and data classificatin to distinguish different types of tissues. In our study two approaches to Raman spectra dimensionality reduction were approbated and as a result we formulated new technique combining both of them: feature filtering based on the selection of those shifts which correspond to the biochemical components providing the statistically significant differences between groups of examined tissues (center of glioblastoma multiforme, tissues from infiltration area and normally appeared white matter) and principal component analysis. We applied the support vector machine to classify tissues after dimensionality reduction of registered Raman spectra. The accuracy of the classification of malignant tissues (tumor edge and center) and normal ones using the principal component analysis alone was 83% with sensitivity of 96% and specificity of 44%. With a combined technique of dimensionality reduction we obtained 83% accuracy with 77% sensitivity and 92% specificity of tumor tissues classification.

Theranostic Properties of Crystalline Aluminum Phthalocyanine Nanoparticles as a Photosensitizer.

The study of phthalocyanines, known photosensitizers, for biomedical applications has been of high research interest for several decades. Of specific interest, nanophotosensitizers are crystalline aluminum phthalocyanine nanoparticles (AlPc NPs). In crystalline form, they are water-insoluble and atoxic, but upon contact with tumors, immune cells, or pathogenic microflora, they change their spectroscopic properties (acquire the ability to fluoresce and become phototoxic), which makes them upcoming agents for selective phototheranostics. Aqueous colloids of crystalline AlPc NPs with a hydrodynamic size of 104 ± 54 nm were obtained using ultrasonic dispersal and centrifugation. Intracellular accumulation and localization of AlPc were studied on HeLa and THP-1 cell cultures and macrophages (M0, M1, M2) by fluorescence microscopy. Crystallinity was assessed by XRD spectroscopy. Time-resolved spectroscopy was used to obtain characteristic fluorescence kinetics of AlPc NPs upon interaction with cell cultures. The photodynamic efficiency and fluorescence quantum yield of AlPc NPs in HeLa and THP-1 cells were evaluated. After entering the cells, AlPc NPs localized in lysosomes and fluorescence corresponding to individual AlPc molecules were observed, as well as destruction of lysosomes and a rapid decrease in fluorescence intensity during photodynamic action. The photodynamic efficiency of AlPc NPs in THP-1 cells was almost 1.8-fold that of the molecular form of AlPc (Photosens). A new mechanism for the occurrence of fluorescence and phototoxicity of AlPc NPs in interaction with cells is proposed.

Analysis of the Results of Severe Intraepithelial Squamous Cell Lesions and Preinvasive Cervical Cancer Phototheranostics in Women of Reproductive Age.

(1) Purpose: To investigate the efficacy and safety of using PDT in the treatment of severe intraepithelial squamous lesions of the cervix and preinvasive cervical cancer associated with HPV in women of reproductive age. (2) Methods: The examination and treatment of 45 patients aged 22-49 years with morphologically confirmed HPV-associated cervical intraepithelial neoplasia of a severe degree (17 patients) and preinvasive cervical cancer (28 patients) were performed. All patients underwent PDT of the cervix using a chlorin e6 photosensitizer; after which, the affected areas of the cervix were evaluated using video and spectral fluorescence diagnostics. PDT effectiveness was assessed on the basis of colposcopy data, a cytological examination of exo- and endocervix and PAP test scrapings or the liquid cytology method, and polymerase chain reaction for HPV carriage 4 weeks after PDT, as well as on the basis of histological and immunohistochemical studies of biopsy materials 5 weeks after PDT. The expression levels of the Ki-67 and p16 markers in the affected areas of the cervix were also assessed. (3) Results. All patients included in the study tolerated the intravenous administration of the photosensitizer well, with no side effects or allergic reactions observed. In 88.2% of patients with CIN III/HSIL and in 85.7% of women with preinvasive cervical cancer, the effect of the treatment was noted after the first PDT procedure, while complete regression of the dysplasia foci was observed in 15 women (88.2%) with CIN III/HSIL and in 25 patients (89.3%) with preinvasive cervical cancer. Partial regression to the form of LSIL/CIN I was noted in two cases (11.8%) in the CIN III/HSIL group and in three cases (10.7%) in the group of patients with preinvasive cervical cancer. After PDT, a statistically significant decrease in the expression of the Ki-67 and p16 levels relative to the initial values was noted. (4) Conclusions. The results obtained indicate the high efficiency of PDT with intravenous administration of the chlorin photosensitizer for the treatment of intraepithelial lesions of the cervix with a selective effect on pathologically altered tissue. The use of this approach makes it possible to preserve the normal anatomical and functional characteristics of the cervix, which is especially important for maintaining the fertility of patients.

Albumin microbubbles conjugated with zinc and aluminum phthalocyanine dyes for enhanced photodynamic activity.

Gas-liquid interfaces are reaching a particular interest in biomedicine. Microbubbles, ultrasound contrast agents of clinical routine, gained increasing attention as theranostic platforms due to the preserved acoustic response, drug conjugation capabilities, and applicability in biological barrier opening. A combination of microbubbles and photodynamic therapy agents can enhance the photodynamic effect, yet the evaluation of agent conjugation on microbubble stabilization and photodynamic effect is needed. Hence, two commercially available phthalocyanine photosensitizers - Holosens® (ZnPc) and Photosens® (AlPc) - were coupled with bovine serum albumin before microbubble synthesis. We demonstrated an albumin: phthalocyanine ratio of 1:1 and covalent attachment for ZnPc, a ratio of 1:3 with electrostatic binding for AlPc. Submicron-sized microbubbles (air- and SF6- filled) had a diameter of 0.8 µm. Albumin-phthalocyanine conjugates increased the microbubble concentration and shelf-life stability compared to plain ones. We hypothesized that phthalocyanine fluorescence lifetime values decreased after conjugation with microbubbles due to narrow distance between conjugates in the shell. Agents based on AlPc demonstrated higher photodynamic activity than agents based on ZnPc, and microbubbles preserved acoustic stability in human blood plasma. The biodistribution of AlPc-conjugated microbubbles was evaluated. We conclude that our microbubble platforms demonstrate greater photodynamic activity and prolonged stability for further applications in photodynamic therapy.

On the mechanisms of photodynamic action of photosensitizers based on polycationic derivatives of synthetic bacteriochlorin against human lung cancer cells A549 (in vitro study).

BACKGROUND: One of the tasks of anticancer photodynamic therapy is increasing the efficacy of treatment of cancer nodes with large (clinically relevant) sizes using near-infrared photosensitizers (PS). We study the photodynamic action against A549 human lung cancer cells using PS based on polycationic derivatives of synthetic bacteriochlorin. METHODS: The efficacy and mechanisms of the photodynamic action of PS based on polycationic derivatives of synthetic bacteriochlorin against A549 lung cancer cells were studied in vitro using immunocytochemical and morphological methods. RESULTS: It was found that PS based on tetracationic and octacationic derivatives of synthetic bacteriochlorin induce necrosis, apoptosis, decreasing of proliferative and mitotic activity, as well as reducing the number of ALDH1-positive cancer cells with signs of stem cells in A549 human lung cancer cell culture. The IC50 values (concentration of a PS that reduces cells survival by 50%) were about 0.69 µM for tetracationic PS and 0.57 µM for octacationic PS under irradiation at 30 J/cm2 while in the "dark" control they were higher than 100 µM for both PSs. CONCLUSIONS: Photosensitizers based on polycationic derivatives of synthetic bacteriochlorin have high phototoxicity against A549 cancer cells caused by the induction of necrosis and apoptosis of cancer cells, including cells with signs of stemness, and a sharp decrease of mitotic and proliferative activity.

A method for intra-percardial PDT for malignant mesothelioma.

We describe a case of a 35-year-old patient with recurrent non-resectable pleural mesothelioma cT4N0M0 with a confirmed malignant pericardial effusion, threatening for cardiac tamponade. We performed and described our experience of intrapericardial photodynamic therapy which was well tolerated and with a good survival result. After 12 months of follow-up our patient showed no signs of pericardial effusion and in stable condition, keeping high level of quality of life. This clinical case is an example of the excellent palliative effect of photodynamic therapy together with concomitant immunotherapy.

Study of synthesis temperature effect onß-NaGdF4: Yb3+, Er3+ upconversion luminescence efficiency and decay time using maximum entropy method.

Upconversion materials have several advantages for many applications due to their great potential in converting infrared light to visible. For practical use, it is necessary to achieve high intensity of UC luminescence, so the studies of the optimal synthesis parameters for upconversion nanoparticles are still going on. In the present work, we analyzed the synthesis temperature effect on the efficiency and luminescence decay ofß-NaGd0.78Yb0.20Er0.02F4(15-25 nm) upconversion nanoparticles with hexagonal crystal structure synthesized by anhydrous solvothermal technique. The synthesis temperature was varied in the 290 °C-320 °C range. The synthesis temperature was shown to have a significant influence on the upconversion luminescence efficiency and decay time. The coherent scattering domain linearly depended on the synthesis temperature and was in the range 13.1-22.3 nm, while the efficiency of the upconversion luminescence increases exponentially from 0.02 to 0.10% under 1 W cm-2excitation. For a fundamental analysis of the reasons for the upconversion luminescence intensity dependence on the synthesis temperature, it was proposed to use the maximum entropy method for luminescence decay kinetics processing. This method does not require a preliminary setting of the number of exponents and, due to this, makes it possible to estimate additional components in the luminescence decay kinetics, which are attributed to different populations of rare-earth ions in different conditions. Two components in the green luminescence and one component in the red luminescence decay kinetics were revealed for nanoparticles prepared at 290 °C-300 °C. An intense short and a weak long component in green luminescence decay kinetics could be associated with two different populations of ions in the surface quenching layer and the crystal core volume. With an increase in the synthesis temperature, the second component disappears, and the decay time increases due to an increase in the number of ions in the crystal core volume and a more uniform distribution of dopants.

The Combined Use of 5-ALA and Chlorin e6 Photosensitizers for Fluorescence-Guided Resection and Photodynamic Therapy under Neurophysiological Control for Recurrent Glioblastoma in the Functional Motor Area after Ineffective Use of 5-ALA: Preliminary Results.

The treatment of glial brain tumors is an unresolved problem in neurooncology, and all existing methods (tumor resection, chemotherapy, radiotherapy, radiosurgery, fluorescence diagnostics, photodynamic therapy, etc.) are directed toward increasing progression-free survival for patients. Fluorescence diagnostics and photodynamic therapy are promising methods for achieving gross total resection and additional treatment of residual parts of the tumor. However, sometimes the use of one photosensitizer for photodynamic therapy does not help, and the time until tumor relapse barely increases. This translational case report describes the preliminary results of the first combined use of 5-ALA and chlorin e6 photosensitizers for fluorescence-guided resection and photodynamic therapy of glioblastoma, which allowed us to perform total resection of tumor tissue according to magnetic resonance and computed tomography images, remove additional tissue with increased fluorescence intensity without neurophysiological consequences, and perform additional therapy. Two months after surgery, no recurrent tumor and no contrast uptake in the tumor bed were detected. Additionally, the patient had ischemic changes in the access zone and along the periphery and cystic-glial changes in the left parietal lobe.

A Pilot Study of Fluorescence-Guided Resection of Pituitary Adenomas with Chlorin e6 Photosensitizer.

Fluorescence diagnostics is one of the promising methods for intraoperative detection of brain tumor boundaries and helps in maximizing the extent of resection. This paper presents the results of a pilot study on the first use of the chlorin e6 photosensitizer and a two-channel video system for fluorescence-guided resection of pituitary adenomas. The study's clinical part involved two patients diagnosed with hormonally inactive pituitary macroadenomas and one patient with a hormonally active one. All neoplasms had different sizes and growth patterns. The data showed accumulation of chlorin e6 in tumor tissues in high concentrations: Patient 1: 2 mg/kg, Patient 2: 5 mg/kg, and Patient 3: 4 mg/kg. For Patient 1, the residual part of the tumor was not resected since it was intimately attached to the anterior genu of the internal carotid artery. For Patients 2 and 3, no regions of increased Ce6 accumulation were detected in the tumor foci after resection. Therefore, the use of the Ce6 and a two-channel video system helped to achieve a high degree of tumor resection in each case.