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Antimicrobial photodynamic therapy (aPDT) was demonstrated to be effective against various species of Gram-positive bacteria. However, the complex structure of a Gram-negative bacteria envelope limits the application of aPDT. Thus, the goal of this study was to improve the efficiency of antimicrobial photodynamic therapy with Fotoditazin against uropathogenic Gram-negative bacteria. The non-ionic detergent Triton X-100 and emulsifier Tween 80 were tested. The effect of extracellular photosensitizer on aPDT efficacy was analyzed. Moreover, the irradiation regime was optimized in terms of the output power and emitting mode. It was found that Triton X-100 at 10% vol enhanced the efficacy of aPDT of E. coli up to 52%. The subsequent observation demonstrated that, when the photosensitizer was removed from the extracellular space, the efficacy of aPDT on various Gram-negative species decreased dramatically. As for the irradiation mode, an increase in the laser output power led to an increase in the aPDT efficacy. The pulsed irradiation mode did not affect the aPDT efficacy. Thus, in order to achieve optimal aPDT efficacy, bacteria should be irradiated at 450-mW output power in the presence of Triton X-100 and a photosensitizer in the extracellular environment. However, it should be noted that the efficacy of aPDT of K. pneumoniae was significantly lower than for other species. The developed aPDT technique may be effective in a native environment of uropathogenic microorganisms. [ABSTRACT FROM AUTHOR]

Background. Photodynamic Therapy is one of the treatment methods used in modern oncology. Evaluation of the efficacy in vivo of photosensitizers on tumor models is generally accepted, but the photodynamic therapy technique in mice is not without drawbacks.The purpose of the study was evaluation of the efficacy of photodynamic therapy in mice with Ehrlich tumor model after subcutaneous and intracutaneous injection of tumor cells.Material and Methods. The study was conducted on BAL B/C mice of both sexes. Fotoditazin® and Radachlorin® were used as photosensitizers. For photoactivation, the Alod laser apparatus with a wavelength of 662 nm was used.Results. A comparison of photodynamic therapy with subcutaneous and intracutaneous localization of Ehrlich tumor was performed. It was shown that depending on the location and depth of inoculation of Ehrlich tumor, the pharmacokinetics (both the fluorescence intensity over time and the contrast ratio of the tumor/surrounding tissue) and pharmacodynamics (tumor growth inhibition, survival) of photosensitizers are significantly different. Higher contrast of the tumor/surrounding tissue is observed with intracutaneous localization of the tumor.Conclusion. A model with intracutaneous localization of Ehrlich tumor can be recommended for a primary assessment of efficacy; it allows the use of fewer animals in the experiment. When planning experiments to study photosensitizers and evaluating their results, the advantages and disadvantages of different methods for modeling tumors in mice should be taken into account.

In this article we submit the case report of a patient with cT1N0M0 penile cancer diagnosis. The patient underwent two courses of photodynamic therapy (PDT) using Fotoditazin photosensitizer (PS) and ATKUS-2 diode laser. The PS was administered at a dose of 1 mg/kg of body weight 2 hours prior to the PDT session. The irradiation parameters were: 662 nm laser wavelength, 200 mW/cm2 power density and 250 J/cm2 energy density. In the presented clinical observation, we demonstrated that PDT is an effective and safe treatment method in patients with non-invasive penile cancer. The use of photodynamic therapy allowed preserving the physiological urination, sexual function and achieving a good cosmetic effect.

Antimicrobial photodynamic therapy (aPDT) was demonstrated to be effective against various species of Gram-positive bacteria. However, the complex structure of a Gram-negative bacteria envelope limits the application of aPDT. Thus, the goal of this study was to improve the efficiency of antimicrobial photodynamic therapy with Fotoditazin against uropathogenic Gram-negative bacteria. The non-ionic detergent Triton X-100 and emulsifier Tween 80 were tested. The effect of extracellular photosensitizer on aPDT efficacy was analyzed. Moreover, the irradiation regime was optimized in terms of the output power and emitting mode. It was found that Triton X-100 at 10% vol enhanced the efficacy of aPDT of E. coli up to 52%. The subsequent observation demonstrated that, when the photosensitizer was removed from the extracellular space, the efficacy of aPDT on various Gram-negative species decreased dramatically. As for the irradiation mode, an increase in the laser output power led to an increase in the aPDT efficacy. The pulsed irradiation mode did not affect the aPDT efficacy. Thus, in order to achieve optimal aPDT efficacy, bacteria should be irradiated at 450-mW output power in the presence of Triton X-100 and a photosensitizer in the extracellular environment. However, it should be noted that the efficacy of aPDT of K. pneumoniae was significantly lower than for other species. The developed aPDT technique may be effective in a native environment of uropathogenic microorganisms.

Currently, photodynamic therapy (PDT) remains the most effective treatment for actinic keratosis (AK). With the increase in the incidence of AK, mainly due to the popularization of recreation in countries with increased insolation, there is an increasing interest in developing new methods of diagnostics and treatment and improving the existing ones. Studies that are aimed at determining the final efficacy of PDT, taking into account the resulting adverse reactions and long-term cosmetic results, are becoming increasingly popular. The nature of the light needed to excite a photosensitizer (PS) opens up new possibilities in the field of experimental studies that are aimed at reducing adverse reactions with similar efficacy of the applied therapy. In the review article, we presented the results of our own and foreign studies on the diagnosis and treatment of AK for 2017–2019, namely: we determined the possibilities of using sources with natural and short-wave radiation at different depths of skin lesions; presented a classification of the growth of AK in the basal layer of the epidermis, which increases the possibility of predicting the outcomes of the disease; showed the prevailing efficiency of fluorescent diagnostics compared with traditional diagnostic methods; evaluated the advantages of PDT using natural light and artificial sources of radiation; described the possibility of using a combination of drugs to increase the effectiveness of PDT in difficult to treat areas and in AK foci with a high degree of damage to the basal layer of the epidermis.

Cytological studies on lymph nodes of abdominal lymphodissection zone after local intraoperative photodynamic therapy (IOPDT) of gastrointestinal cancers were carried out. As a result of the PDT, the metastatic cells are destroyed, their cytoplasmic membranes and the cytoplasm disappears, leaving behind interphase nuclei ("naked nuclei") (p

The article shows possibilities in fluorescence imaging of malignant skin tumors with chlorin series photosensitizers (PS) photolon and fotoditazin. The regularities of photosensitizer accumulation from the data of local fluorescence spectroscopy depending on the PS and its dose, the clinical picture and the histological form of the malignant skin neoplasm is investigated. It is shown that the level and selectivity of PS accumulation in the tumor focus depends on the PS dose. In studies on 10 patients with basal cell skin cancer after the introduction of fotoditazin at a dose less than 1 mg/kg, fluorescent contrast between tumor and healthy tissue varied between 1.3 and 9.5, the average was 2.8±0.3; for patients who had the administered fotoditazin dose of 1 mg/kg, fluorescent contrast was 2.9±0.4, varying from 1.4 to 5. In a study with 127 patients after the introduction of photolon in the dose of 0.7-1 mg/kg, the average value of the fluorescence intensity in relative units in the intact skin was 6.9±0.3 (min 4.6, max 12.2), at a dose of 1.1 to 1.4 mg/kg – 8.0±0.3 (min 4.6, max 12.5), at a dose of 1.5-2 mg/kg – 9.9±0.7 (min 5.7, max 20.3). It is also shown that fluorescence intensity of malignant neoplasm of the skin with the same dose of the photosensitizer depends on the neoplasm’s clinical and histological forms. So, 3 hours after the introduction of photolon at a dose of 1.3 mg/kg the average fluorescent contrast in the surface type of skin cancer was 2.7±0.5, in the nodal form – 2.3±0.2, in erosive-ulcerative form – 3.6±0.3. In patients with nodular form of squamous skin cancer after the introduction of photolon at a dose of 1.3 mg/kg fluorescent contrast was significantly higher (p

A case of successful photodynamic therapy of residual laryngeal tumor after external beam radiotherapy (EBRT) is reported. The female patient with diagnosis of laryngeal cancer T1N0M0 underwent a course of EBRT on larynx, fraction dose = 2 Gy, 5 fractions per week, total radiation dose = 60 Gy. One month after EBRT the continued growth of residual tumor in the left vocal fold was diagnosed. The patient had 4 courses of photodynamic therapy with photosensitizer fotoditazin at a dose of 100 mg combined with electroresection of residual laryngeal tumor. The control video-assisted laryngoscopy 1 month after the 4th course of photodynamic therapy showed that larynx was flexible, vocal function was fully restored, tumor of the left vocal fold wasn’t detected. Non-recurrence follow-up period is 10 month. The patient is under follow-up.

The results of the experimental study of immune response of human skin malignant melanoma cells Mel 226 on photodynamic exposure are represented in the article. Photoinduced apoptosis of skin malignant melanoma was studied in vitro. The study showed that irradiation with the agent fotoditazin at dose of 0.5–2.5 µg/ml (6 and 10 min exposure 30 min before irradiation; irradiation parameters: wavelength of 662 nm, total light dose from 40 to 60 J/cm2) induced early apoptosis. The increase of the time of laser irradiation significantly accelerates the conversion of photosensitized tumor cells from early to late apoptosis.

The review is on opportunities and possibilities of application of photodynamic therapy in clinical practice. The advantages of this method are the targeting of effect on tumor foci and high efficiency along with low systemic toxicity. The results of the set of recent Russian and foreign clinical trials are represented in the review. The method is successfully used in clinical practice with both radical (for early vulvar, cervical cancer and pre-cancer, central early lung cancer, esophageal and gastric cancer, bladder cancer and other types of malignant tumors), and palliative care (including tumor pleuritis, gastrointestinal tumors and others). Photodynamic therapy delivers results which are not available for other methods of cancer therapy. Thus, photodynamic therapy allows to avoid gross scars (that is very important, for example, in gynecology for treatment of patients of reproductive age with cervical and vulvar cancer), delivers good cosmetic effect for skin tumors, allows minimal trauma for intact tissue surrounding tumor. Photodynamic therapy is also used in other fields of medicine, such as otorhinolaryngology, dermatology, ophthalmology, orthopaedics, for treatment of papilloma virus infection and purulent wounds as antibacterial therapy.

The results of the clinical observation of a female patient with squamous cell carcinoma of the cheek skin treated by the method of photodynamic therapy (PDT) using the photosensitizer of fotoditazin are represented. The patient had single course of PDT. Fotoditazin was injected in a dose of 0.8 mg/kg of body weight as a single intravenous infusion in 0.9% sodium chloride. The irradiation was performed once, 2.5 h after injection of the photosensitizer (power density of laser irradiation – 200-300 mW/cm2, light dose of a single session of 300-350 J/ cm2). There were no side effects after photosensitizer injection and after irradiation. The result of the treatment was defined as partial tumor regression. For nowadays the follow-up period is 2 months. The repeated course of PDT is scheduled.

Results of efficiency assessment of different diagnosis for preinvasive cervical lesions are represented in the article. During investigation the retrospective analysis of 353 patient histories of women with cervical intraepithelial neoplasia (primary and recurrent), who have been observed in Ivanovskiy regional oncological dispensary from 2002 to 2011, was performed. The accuracy rates of diagnosis of cervical intraepithelial neoplasia for one or several methods including cytological study, colposcopy and fluorescence cystoscopy were compared. Fluorescence diagnosis was performed with drug fotoditazin (LLC «VETA-GRAND», marketing authorisation №LS 001246) at dose of 1,0 mg/kg body weight. The final diagnosis was determined by results of histological study. The accuracy of cytological study accounted for 67,5–80,7%. Using colposcopy the exact diagnosis was determined in 67,9–74,4% of cases. Combination of cytological study with colposcopy improved the accuracy of diagnosis up to 82.1–88.9%. The superior results were for concurrent use of cytological study with colposcopy and fluorescence diagnosis – in such case the diagnosis was correct in 92,0–96,7% of patients. The analysis of results showed that using all methods of diagnosis the accuracy of diagnosis for recurrent cervical intraepithelial neoplasia was lower than for primary lesions. The decrease of diagnosis accuracy is probably related to previous diagnosis and therapeutic manipulations on cervix. Thus, multimodal diagnosis investigation with methods of fluorescence spectroscopy allows to improve accuracy of diagnosis for preinvasive cervical lesions.

Comprehensive study for optimization of parameters of photodynamic action with fotoditazin in patients with tumor and pre-tumor cervical diseases was conducted. The study included 52 female patients: pre-invasive cervical diseases were diagnosed in 34 (CIN I – in 9, CIN II – in 13, CIN III – in 12), cervical cancer – in 11 (8 had squamous cell cancer, 3 – adenocarcinoma of cervical canal), chronic cervicitis – in 7. The study agent in the form of 0,5% gel was applied on cervix in dose of 1 ml. To detect optimal interval between gel application and conduction of photodynamic therapy dynamics of accumulation and elimination of photosensitizer by means of its fl uorescence was studied. Fotoditazin was shown to have good accumulation in pathological tissues. The maximal agent accumulation was noticed in 30 min, continued about 15 min, and then gradually decreased. Maximal fl uorescence of photosensitizer was observed in foci of malignant tumor and severe intraepithelial neoplasia. To detect optimal light dose for irradiation cytological study of cell smear from specimen after light exposure with different light doses was performed. The minimal light dose necessary for activation of photochemical reaction pathway was 100 J/cm2, and optimal – 250 J/cm2. This dose allowed to destroy all atypical cells in the area of light exposure after application of gel fotoditazin. According to obtain data we suppose that the most effi cient regimen of photodynamic therapy with local application of fotoditazin-gel for treating dysplasia and pre-invasive cervical cancer was a dose of laser irradiation of 250 J/cm2 with duration of application of 30–45 min.

Pilot studies of pharmacokinetics and pharmacodynamics of new photosensitizer liposomal boronated chlorine in mice with melanoma В16 were performed. Dynamics of drug accumulation in tumor and normal tissue (level of accumulation in tissues was assessed by means of fl uorescence) was studied. For intraperitoneal injection at a dose of 5 mg/kg the drug was shown to accumulate gradually in tumor and normal tissues with maximal fl uorescence values in 2–3 h after injection. Then fl uorescence intensity in tissues gradually decreased, achieving nearly initial base-line in 120 h after beginning of the study. The hotosensitizer accumulated in tumor tissue with average selectivity: contrast index for maximal drug accumulation in tissues accounted for 1.7–2.8. According to obtained data for following research the time interval between drug injection and irradiation of 3h was chosen. On the second stage of the study dependence of photodynamic therapy effi cacy on different parameters including photosensitizer dose for intraperitoneal injection (5–10 mg/kg), light dose (150–300 J/cm2) and power density (0.25–0.51 mW/cm2). The irradiation was performed by semiconductor laser on wavelength of 662±1 nm. The effi cacy was maximal for following regimen: photosensitizer dose of 5 mg/kg, light dose of 300 J/cm2, power intensity of 0.44 mW/cm2. For this regimen at the end of follow-up (21 days) complete tumor regression was obtained in 75% of animals and average coeffi cient of absolute tumor growth accounted for only 7.82.

The main stages of development and establishment of photodynamic therapy (PDT) in Russia are described in the article. Brief description of photosensitizers approved for clinical use in Russia including fotogem, photosens, alasens, radachlorine and fotoditazin is represented. Their physical and chemical and spectral characteristics, drug formulations, results of pre-clinical studies and post-marketing experience are shown. Main research centers dealing with PDT are listed.

Results of local fluorescence spectroscopy in 185 women with underlying and pre-invasive disease of cervix and high-risk HPV infection are represented. Fluorescence study was performed 2h after intravenous injection of fotoditazin in a dose of 1 mg/kg (wavelength 636.5 nm). Accumulation of the photosensitizer was estimated by diagnostic parameter (DP) value, calculated as mean value of fluorescence scaled to each type of tissue. For normal tissues DP accounted for 0.6±0.4, showing accumulation of the photosensitizer. According to the study the medication did not also accumulate in retention cysts (DP 0.3±0.1), explaining low efficiency of photodynamic therapy for this pathology. The accumulation of fotoditazin depends significantly on type of pathologic tissue. In patients with inflammation, leukoplakia and CIN I accumulation of the photosensitizer in pathologic foci was negligible: DP accounted for 1.7±0.2, 1.8±0.2 and 2.1±0.3, respectively. In sites of endometriosis and CIN II DP was significantly higher and accounted for 8.3±2.1 and 14.1±4.1, respectively. The greatest accumulation of the photosensitizer was registered in sites of CIN III, squamous cell carcinoma and adenocarcinoma. Though DP value for these pathologies had almost no difference and accounted for 23.1±4.7, 22.7±1.8 and 23.3±1.4, respectively. For fluorescence diagnosis of severe dysplasia in 48% of patients borders of fluorescence regions were beyond lesions detected for extended colposcopy with additional areas of fluorescence. Targeted biopsy of these regions proved pathology in all patients: CIN II, CIN III, mild dysplasia or CIS. Thus, local spectroscopy allows to diagnosis multifocal lesions on cervix, to define correctly borders of lesion and consider excisional biopsy in-time.

The results of the clinical observation of patient with recurrent basal cell skin carcinoma of the parietal region occurred in 4 years after radiation therapy are represented. The patient underwent photodynamic therapy (PDT) using photosensitizer fotoditazin at a dose of 1.0 mg/kg; the laser power density was 0.45 W/cm2 , the laser energy density – 300 J/cm2 . Tolerability of the treatment was satisfactory. One year after treatment there was a cosmetically satisfying soft normotrophic scar with no attachment to underlying tissues in the site of the treatment of basal cell carcinoma. According to cytological study tumor cells were not detected. For five-year follow-up there was no recurrence.