Use Of 5-aminolevulinic Acid Research Articles

Efficacy of photodynamic therapy using 5-aminolevulinic acid-induced photosensitization is enhanced in pancreatic cancer cells with acquired drug resistance

The use of 5-aminolevulinic acid (ALA) as a precursor for protoporphyrin IX (PpIX) is an established photosensitization strategy for photodynamic therapy (PDT) and fluorescence guided surgery. Ongoing studies are focused on identifying approaches to enhance PpIX accumulation as well as to identify tumor sub-types associated with high PpIX accumulation. In this study, we investigated PpIX accumulation and PDT treatment response with respect to nodule size in 3D cultures of pancreatic cancer cells (Panc1) and a derivative subline (Panc1OR), which has acquired drug resistance and exhibits increased epithelial mesenchymal transition. In monolayer and 3D culture dose response studies the Panc1OR cells exhibit significantly higher cell killing at lower light doses than the drug naïve cells. Panc1OR also exhibits increased PpIX accumulation. Further analysis of cell killing efficiency per molecule of intracellular PpIX indicates that the drug resistant cells are intrinsically more responsive to PDT. Additional investigation using exogenous delivery of PpIX also shows higher cell killing in drug resistant cells, under conditions which achieve approximately the same intracellular PpIX. Overall these results are significant as they demonstrate that this example of drug-resistant cells associated with aggressive disease progression and poor clinical outcomes, show increased sensitivity to ALA-PDT.

Advantage and challenges in the use of 5-Aminolevulinic acid (5-ALA) in neurosurgery.

Advantage and challenges in the use of 5-Aminolevulinic acid (5-ALA) in neurosurgery.

Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study.

Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.

Severe hypotension and postoperative cardiac arrest caused by 5-aminolevulinic acid: a case report

BackgroundAlthough 5-aminolevulinic acid is useful for the photodynamic diagnosis of bladder tumors, it often causes severe intraoperative hypotension. We report a case of postoperative cardiac arrest in addition to severe intraoperative hypotension, probably owing to the use of 5-aminolevulinic acid.Case presentationAn 81-year-old Japanese man was scheduled to undergo transurethral resection of bladder tumor. The patient took 5-aminolevulinic acid orally 2 hours before entering the operating room. After the induction of anesthesia, his blood pressure decreased to 47/33 mmHg. The patient’s hypotension did not improve even after noradrenaline was administered. After awakening from anesthesia, the patient’s systolic blood pressure increased to approximately 100 mmHg, but approximately 5 hours after returning to the ward, cardiac arrest occurred for approximately 12 seconds.ConclusionWe experienced a case of postoperative cardiac arrest in a patient, probably owing to the use of 5-aminolevulinic acid. Although the cause of cardiac arrest is unknown, perioperative hemodynamic management must be carefully performed in patients taking 5-aminolevulinic acid.

The use of 5-aminolevulinic acid (5-ALA) in high-grade glioma surgery, a single Canadian center experience

The use of 5-aminolevulinic acid (5-ALA) in high-grade glioma surgery, a single Canadian center experience

Antibacterial effects against pathogens of Vibrio genus using 5-aminolevulinic acid produced from recombinant Escherichia coli

BackgroundVibrio genus comprises a group of notorious pathogens that cause diseases in aquatic animals, leading to a reduction in seafood production. With climate change, Vibrio spp. pose an increasingly severe threat to the growing aquaculture industry, thereby affecting global food production. This study explored the use of 5-aminolevulinic acid (5-ALA) as a biocompatible antibacterial agent due to the inducibility of antibacterial properties by light and in vivo conversion to photosensitizing protoporphyrin IX (PPIX). Methods5-ALA were produced by recombinant E. coli was introduced as a photodynamic therapy against three Vibrio strains; namely, Vibrio parahaemolyticus (Vp), Vibrio alginolyticus (Va), and Vibrio damsela (Vd). The effect of 5-ALA on the three Vibrio species was investigated at a neutral pH, considering various factors such as reaction time and concentration under both light and dark conditions. Significant findingsThe antimicrobial photodynamic therapy (aPDT) utilizing 0.5 % (w/v) 5-ALA was effective against Vibrio sp. only at pH < 5.5. In a neutral pH environment and without light exposure, antimicrobial activity was still observed against V. alginolyticus and Vibrio parahaemolyticus when the concentration of 5-ALA was increased to 1 % and 2 %, respectively. The bactericidal effect was only 39 % for Vibrio damsela, indicating a slower biosynthesis of PPIX. Nonetheless, this also suggests the potential of 5-ALA as an in vitro antibacterial agent under acidic conditions. The bactericidal effect of crude and pure 5-ALA was found to be similar, indicating the potential of using cost-effective crude extracts as aPDT agent.

How Reliable Is Fluorescence-Guided Surgery in Low-Grade Gliomas? A Systematic Review Concerning Different Fluorophores.

Fluorescence-guided surgery has been increasingly used to support glioma surgery with the purpose of obtaining a maximal safe resection, in particular in high-grade gliomas, while its role is less definitely assessed in low-grade gliomas. A systematic review was conducted. 5-aminolevulinic acid, sodium fluorescein, indocyanine green and tozuleristide were taken into account. The main considered outcome was the fluorescence rate, defined as the number of patients in whom positive fluorescence was detected out of the total number of patients. Only low-grade gliomas were considered, and data were grouped according to single fluorophores. 16 papers about 5-aminolevulinic acid, 4 about sodium fluorescein, 2 about indocyanine green and 1 about tozuleristide were included in the systematic review. Regarding 5-aminolevulinic acid, a total of 467 low-grade glioma patients were included, and fluorescence positivity was detected in 34 out of 451 Grade II tumors (7.3%); while in Grade I tumors, fluorescence positivity was detected in 9 out of 16 cases. In 16 sodium fluorescein patients, seven positive fluorescent cases were detected. As far as indocyanine is concerned, two studies accounting for six patients (three positive) were included, while for tozuleristide, a single clinical trial with eight patients (two positive) was retrieved. The current evidence does not support the routine use of 5-aminolevulinic acid or sodium fluorescein with a standard operating microscope because of the low fluorescence rates. New molecules, including tozuleristide, and new techniques for fluorescence detection have shown promising results; however, their use still needs to be clinically validated on a large scale.

P.110 The use of 5-Aminolevulinic acid (5-ALA) in high-grade glioma surgery, a single Canadian center experience

Background: 5-Aminolevulinic acid (5-ALA) is a prodrug used to selectively illuminate high-grade glioma (HGG) tissue intra-operatively, shown to nearly double complete resection rates in a 2006 multicentre, phase III clinical trial. Here, we review the history of the 2020 approval of 5-ALA in Canada and present some of the first preliminary results on resection rates, survival analysis, and adverse effects from a single Canadian center. Methods: We enrolled 76 patients (median age 61 years, 42 male) with suspected HGG amenable to surgical resection between June 2020 and January 2023. Gross total resection was defined by the absence of enhancing lesions on postoperative MRI. We compared the survival distributions of confirmed HGG cases with complete vs. incomplete resection using a log-rank test and Kaplan-Meier statistic. Results: 52 patients were confirmed as having a HGG based on a pathological diagnosis. In 32 of these patients (60.3%) a gross total resection was achieved. 82.76% were still alive at 180 and 270 days, and 72.73% at 360 days. 47.8% had a survival of 600 or more days. Conclusions: 5-ALA fluorescence-guided surgery resulted in high complete resection rates, and improved overall survival comparable to the literature with no notable adverse side effects.

5-Aminolevulinic Acid and Red Led in Endodontics: A Narrative Review and Case Report.

The present study aims to discuss the main factors involving the use of 5-aminolevulinic acid together with red LED light and its application in endodontic treatment through a narrative review and a case report. Persistence of microorganisms remaining on chemical-mechanical preparation or intracanal dressing is reported as the leading cause of failure in endodontics. Photodynamic therapy has become a promising antimicrobial strategy as an aid to endodontic treatment. Being easy and quick to apply, it can be used both in a single session and in several sessions, as well as not allowing forms of microbial resistance. 5-aminolevulinic acid in combination with red LED light has recently been studied in many branches of medicine, with good results against numerous types of bacteria including Enterococuss faecalis. The case report showed how bacterial count of CFU decreased by half (210 CFU/mL), after 45 min of irrigation with a gel containing 5% of 5-aminolevulinic acid compared to the sample before irrigation (420 CFU/mL). The subsequent irradiation of red LED light for 7 min, the bacterial count was equal to 0. Thus, it is concluded that the use of 5-aminolevulinic acid together with red LED light is effective in endodontic treatment.

Anatomical distribution of cancer stem cells between enhancing nodule and FLAIR hyperintensity in supratentorial glioblastoma: time to recalibrate the surgical target?

It is ge nerally accepted that glioblastoma (GBM) arise from cancer stem cells (CSC); however, there is little evidence on their anatomical distribution. We investigated the expression and distribution of SOX-2-positive and CD133-positive CSCs both in the enhancing nodule (EN) of GBM and in the FLAIR hyperintensity zones on a surgical, histopathological series of 33 GBMs. The inclusion criterion was the intraoperative sampling of different tumor regions individualized, thanks to neuronavigation and positivity to intraoperative fluorescence with the use of 5-aminolevulinic acid (5-ALA). Thirty-three patients (20 males and 13 females with a mean age at diagnosis of 56years) met the inclusion criterion. A total of 109 histological samples were evaluated, 52 for ENs and 57 for FLAIR hyperintensity zone. Considering the quantitative distribution of levels of intensity of staining (IS), ES (extent score), and immunoreactivity score (IRS), no difference was found between ENs and FLAIR regions for both the SOX-2 biomarker (respectively, IS p = 0.851, ES p = 0.561, IRS p = 1.000) and the CD133 biomarker (IS p = 0.653, ES p = 0.409, IRS p = 0.881). This evidence suggests to recalibrate the target of surgery for FLAIRECTOMY and 5-ALA could improve the possibility to achieve this goal.

5-ALA-guided tumor resection during awake speech mapping in gliomas located in eloquent speech areas: Single-center experience.

BackgroundAchieving maximal functionally safe resection of gliomas located within the eloquent speech areas is challenging, and there is a lack of literature on the combined use of 5-aminolevulinic acid (5-ALA) guidance and awake craniotomy.ObjectiveThe aim of this study was to describe our experience with the simultaneous use of 5-ALA fluorescence and awake speech mapping in patients with left frontal gliomas located within the vicinity of eloquent speech areas.Materials and methodsA prospectively collected database of patients was reviewed. 5-ALA was administered at a dose of 20 mg/kg 2 h prior to operation, and an operating microscope in BLUE400 mode was used to visualize fluorescence. All patients underwent surgery using the “asleep–awake–asleep” protocol with monopolar and bipolar electrical stimulation to identify the proximity of eloquent cortex and white matter tracts and to guide safe limits of resection along with fluorescence guidance. Speech function was assessed by a trained neuropsychologist before, during, and after surgery.ResultsIn 28 patients operated with cortical mapping and 5-ALA guidance (12 Grade 4, 6 Grade 3, and 10 Grade 2 gliomas), Broca’s area was identified in 23 cases and Wernicke’s area was identified in 5 cases. Fluorescence was present in 14 cases. Six tumors had residual fluorescence due to the positive speech mapping in the tumor bed. Transient aphasia developed in 14 patients, and permanent aphasia developed in 4 patients. In 6 patients operated with cortical and subcortical speech mapping and 5-ALA guidance (4 Grade 4, 1 Grade 3, and 1 Grade 2 gliomas), cortical speech areas were mapped in 5 patients and subcortical tracts were encountered in all cases. In all cases, resection was stopped despite the presence of residual fluorescence due to speech mapping findings. Transient aphasia developed in 6 patients and permanent aphasia developed in 4 patients. In patients with Grade 2–3 gliomas, targeted biopsy of focal fluorescence areas led to upgrading the grade and thus more accurate diagnosis.Conclusion5-ALA guidance during awake speech mapping is useful in augmenting the extent of resection for infiltrative high-grade gliomas and identifying foci of anaplasia in non-enhancing gliomas, while maintaining safe limits of functional resection based on speech mapping. Positive 5-ALA fluorescence in diffuse Grade 2 gliomas may be predictive of a more aggressive disease course.

5-aminolevulinic acid and sodium fluorescein in IV ventricle ependymoma surgery: preliminary experience comparing the two techniques

PurposeThe aim of this study is to compare the use of 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) in IV ventricular ependymoma (IVEP) surgical resection.MethodsIn this retrospective study, six patients with IVEP were enrolled. Gender ratio 2:1 male to female, with mean age 38.9 years old. A 5-ALA oral dose of 20 mg/kg and a SF intravenous dose of 2 mg/kg were administered. Telo-velar approach, operative microscope, and intraoperative monitoring were used in all the operations. We retrospectively compared the two fluorescence techniques at four steps during the surgical procedure: step 1: exposure of the tumor; step 2: dissection of the lesion from the cerebellum; step 3: assessment of the tumor borders and differentiation from normal tissue at the base of implants; and step 4: evaluation of possible residual tissue in the surgical cavity.ResultsAt the first step, the ependymomas resulted well delineated by both fluorescent agents. In this step, 5-ALA was particularly helpful in the case of recurrent ependymoma. At step 2, 5-ALA provided a better identification of the ependymoma boundaries and distinction from cerebellum hemispheres than SF. In steps 3 and 4, SF was really helpful to detect tumor tissue.ConclusionAccording to our experience, fluorescence-guided surgery of IVEP with 5-ALA and SF is useful to maximize surgical resection with less risk of brainstem injury. Both fluorescence techniques are helpful in different steps of IVEP resection. However, further studies are needed to confirm our preliminary data.

Intraoperative Ultrasound: Emerging Technology and Novel Applications in Brain Tumor Surgery.

Intraoperative ultrasound (IOUS) is becoming progressively more common during brain tumor surgery. We present data from our case series of brain tumor surgery performed with the aid of IOUS in order to identify IOUS advantages and crucial aspects that may improve the management of neurosurgical procedures for brain tumors. From January 2021 to September 2021, 17 patients with different brain tumors underwent brain tumor surgery aided by the use of IOUS. During surgery, the procedure was supported by the use of multiples ultrasonographic modalities in addition to standard B-mode: Doppler, color Doppler, elastosonography, and contrast-enhanced intraoperative ultrasound (CEUS). In selected cases, the use of IOUS during surgical procedure was combined with neuronavigation and the use of intraoperative fluorescence by the use of 5-aminolevulinic acid (5-ALA). In one patient, a preoperative ultrasound evaluation was performed through a former iatrogenic skull defect. This study confirms the role of IOUS in maximizing the EOR, which is strictly associated with postoperative outcome, overall survival (OS), and patient’s quality of life (QoL). The combination of ultrasound advanced techniques such as Doppler, color Doppler, elastosonography, and contrast-enhanced intraoperative ultrasound (CEUS) is crucial to improve surgical effectiveness and patient’s safety while expanding surgeon’s view.

The Evolution of 5-Aminolevulinic Acid Fluorescence Visualization: Time for a Headlamp/Loupe Combination

The use of 5-aminolevulinic acid (5-ALA) for intraoperative protoporphyrin IX fluorescent imaging in the resection of malignant gliomas has been demonstrated to improve tumor visualization, increase the extent of resection, and extend progression-free survival. The current technique for visualization of 5-ALA consists of excitation and emission filters built into the operating microscope. However, there are notable limitations to this process, including low quantum yield, expense, and masking of surrounding anatomy. We present 3 cases in which 3 separate methods were employed for visualizing fluorescence. The devices reported are 1) a low-cost blue light flashlight, 2) a low-cost headlamp, and 3) the first reported case of the new Designs for Vision REVEAL Fluorescence-Guided Surgery (FGS) 5-ALA fluorescent headlight and loupes. The aim of the study is to provide confirmation that tumor fluorescence can be observed using commercially available products other than the microscope. We demonstrate through 3 intraoperative cases that a variety of devices can produce visible fluorescence of the high-grade tumor and allow for simultaneous real-time visualization of the adjacent brain parenchyma and vasculature. The REVEAL FGS system appears to offer increased fluorescence emission compared with all other methods, including the microscope. Our study demonstrates the feasibility of using blue/ultraviolet light supplied by a commercially available, inexpensive flashlight or headlamp to visualize 5-ALA fluorescence in high-grade gliomas. We also provide the first documentation of the intraoperative use of the new Designs for Vision REVEAL FGS 5-ALA fluorescent headlight and loupes and report on the experience. Lack of an operative microscope capable of fluorescent illumination should not be a limiting factor in performing fluorescent-guided glioma resection.

Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Patients with Chronic Graft-versus-Host Disease: A First-in-Human Study.

Extracorporeal photopheresis (ECP), an immunomodulatory therapy for the treatment of chronic graft-versus-host disease (cGvHD), exposes isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light to induce the apoptosis of T-cells and, hence, to modulate immune responses. However, 8-MOP-ECP kills diseased and healthy cells with no selectivity and has limited efficacy in many cases. The use of 5-aminolevulinic acid (ALA) and light (ALA-based photodynamic therapy) may be an alternative, as ex vivo investigations show that ALA-ECP kills T-cells from cGvHD patients more selectively and efficiently than those treated with 8-MOP-ECP. The purpose of this phase I-(II) study was to evaluate the safety and tolerability of ALA-ECP in cGvHD patients. The study included 82 treatments in five patients. One patient was discharged due to the progression of the haematological disease. No significant persistent changes in vital signs or laboratory values were detected. In total, 62 adverse events were reported. Two events were severe, 17 were moderate, and 43 were mild symptoms. None of the adverse events evaluated by the internal safety review committee were considered to be likely related to the study medication. The results indicate that ALA-ECP is safe and is mainly tolerated well by cGvHD patients.

Fluorescence-Guided Surgery in the Surgical Treatment of Gliomas: Past, Present and Future.

Simple SummaryGliomas are aggressive central nervous system tumours. The emergence and recent widespread adoption of 5-aminolevulinic acid and fluorescence guided surgery have improved the extent of resection, with implications for improved survival and progression-free survival. This review describes the history, rationale and mechanism behind the use of 5-aminolevulinic acid and fluorescence-guided surgery. We also discuss current limitations and future directions for this important adjunct to glioma surgery. This review aims to provide readers with an up-to-date overview and evidence base on this important topic.Gliomas are central nervous systems tumours which are diffusely infiltrative and difficult to treat. The extent of surgical resection is correlated with improved outcomes, including survival and disease-free progression. Cancerous tissue can be directly visualised intra-operatively under fluorescence by administration of 5-aminolevulinic acid to the patient. The adoption of this technique has allowed surgeons worldwide to achieve greater extents of resection, with implications for improved prognosis. However, there are practical limitations to use of 5-aminolevulinic acid. New adjuncts in the field of fluorescence-guided surgery aim to improve recognition of the interface between tumour and brain with the objective of improving resection and patient outcomes.

Let Me See: Correlation between 5-ALA Fluorescence and Molecular Pathways in Glioblastoma: A Single Center Experience.

Background: Despite the aggressiveness of multimodal treatment, glioblastoma (GBM) is still a challenge for neurosurgeons, neurooncologists, and radiotherapists. A surgical approach is still a cornerstone in GBM therapeutic management, as the extent of resection is strongly related both to overall survival and progression-free survival. From this perspective, the use of photodynamic molecules could represent an interesting tool to achieve maximal and safe resection. Being able to trace the lesion’s edges, indeed, could allow to improve the extent of resection and to minimize residual tumor while sparing normal tissue. The use of 5-aminolevulinic acid (5-ALA) as a photodynamic tracer is well established due to its strict correlation both with cellularity and metabolic activity of the GBM cell clones. Objective: Our study aims to define whether a different molecular asset of GBM (especially investigating IDH 1/2 mutation, proliferation index, and MGMT promoter methylation) results in different fluorescence expression, possibly because of differences in metabolic pathways due to different genotypes. Methods: Patients undergoing surgery for GBM removal at our Institute (Dep. Of Neurosurgery, Ospedale Città della Salute e della Scienza, University of Turin, Italy) were retrospectively reviewed. Patients with histological diagnosis confirmation and to whom 5-ALA was given before surgery were included. The whole surgical procedure was recorded and then analyzed by three different people (a medical student, a resident, and a senior surgeon with an interest in neurooncology and experience in using 5-ALA) and a score was assigned to the different degrees of intraoperative fluorescence. The degree of fluorescence was then matched with the genotype. Results: A trend of grade 2 fluorescence (i.e., ”strong”) was observed in the IDH 1/2 wild-type (WT) genotype, suggesting a more intense metabolic activity in this particular subgroup, while, no or weak fluorescence was observed more often in the IDH 1/2 mutated tumors, suggesting a lower metabolic activity. No relations were found between fluorescence grade and MGMT promoter methylation or, interestingly, cellularity. As a secondary analysis, more epileptogenicity of the IDH 1/2 mutated GBM was noticed, similarly to other recent literature. Conclusion: Our results do not support the use of 5-ALA as a diagnostic tool, or a way to substitute the molecular profiling, but confirm 5-ALA as a powerful metabolic tracer, able to easily detect the pathological cells, especially in the IDH WT genotype, and in this perspective, further studies will be necessary to better describe the metabolic activity of GBM cells.

Systematic Review and Meta-Analysis of In Vitro Anti-Human Cancer Experiments Investigating the Use of 5-Aminolevulinic Acid (5-ALA) for Photodynamic Therapy.

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT.

Characteristics of Fluorescent Intraoperative Dyes Helpful in Gross Total Resection of High-Grade Gliomas-A Systematic Review.

Background: A very important aspect in the treatment of high-grade glioma is gross total resection to reduce the risk of tumor recurrence. One of the methods to facilitate this task is intraoperative fluorescence navigation. The aim of the study was to compare the dyes used in this technique fluorescent intraoperative navigation in terms of the mechanism of action and influence on the treatment of patients. Methods: The review was carried out on the basis of articles found in PubMed, Google Scholar, and BMC search engines, as well as those identified by searched bibliographies and suggested by experts during the preparation of the article. The database analysis was performed for the following phrases: “glioma”, “glioblastoma”, “ALA”, “5ALA”, “5-ALA”, “aminolevulinic acid”, ”levulinic acid”, “fluorescein”, “ICG”, “indocyanine green”, and “fluorescence navigation”. Results: After analyzing 913 citations identified on the basis of the search criteria, we included 36 studies in the review. On the basis of the analyzed articles, we found that 5-aminolevulinic acid and fluorescein are highly effective in improving the percentage of gross total resection achieved in high-grade glioma surgery. At the same time, the limitations resulting from the use of these methods are marked—higher costs of the procedure and the need to have neurosurgical microscope in combination with a special light filter in the case of 5-aminolevulinic acid (5-ALA), and low specificity for neoplastic cells and the dependence on the degree of damage to the blood–brain barrier in the intensity of fluorescence in the case of fluorescein. The use of indocyanine green in the visualization of glioma cells is relatively unknown, but some researchers have suggested its utility and the benefits of using it simultaneously with other dyes. Conclusion: The use of intraoperative fluorescence navigation with the use of 5-aminolevulinic acid and fluorescein allows the range of high-grade glioma resection to be increased.

Study of possibility of cell recognition in brain tumors.

The brain has an exceptionally high requirement for energy metabolism, with glucose serving as the exclusive energy source. Cancers, including glioblastoma, have a high glucose uptake and rely on aerobic glycolysis for energy metabolism. The alternation of high-efficiency oxidative phosphorylation to a low-efficiency aerobic glycolysis pathway (Warburg effect) provides macromolecules for biosynthesis and proliferation. Current research indicates that the specific metabolism in the tumor tissue and normal brain tissue in the glioma allows the use of 5-aminolevulinic acid (5 ALA)-induced protoporphyrin IX (PpIX) and methylene blue (MB) to monitor and correct the development of the tumor. The focus is on the detection of the differences between tumor cells and tumor-associated macrophages/microglia using spectroscopic and microscopic methods, based on the fluorescent signals and the difference in the drug accumulation of photosensitizers (PSs). Since 5 ALA has long been used effectively in the clinic for fluorescent surgical navigation, it was employed as an agent to identify the localization of tumor tissue and study its composition, particularly tumor and immune cells (macrophages), which have also been shown to actively accumulate PpIX. However, since PpIX is photodynamically active, it can be considered effective as the main target of tumor tissue for further successful photodynamic therapy. MB was employed to visualize resident microglia, which is important for their activation/deactivation to prevent the reprogramming of the immune cells by the tumor. Thus, using two drugs, it is possible to prevent crosstalk between tumor cells and the immune cells of different geneses.