The research is devoted to development and study of photosensitizers on a base of injectable nanoparticular formulations of phthalocyanine derivatives absorbing at long wavelength (near-infrared) range of 710–740 nm: Thiosens [liposomal form of aluminum hydroxide 1,8,15,22-tetrakis(phenylsulfanyl)phthalocyanine] and Octasens [polymeric micellar form of zinc 1,4,8,11,15,18,22,25-octachloro-2,3,9,10,16,17,23,24-octakis-(decylsulfanyl)phthalocyanine based on domestic poloxamer Emuxol-268]. Experiments have shown that the photosensitizers under study show high selectivity of accumulation and prolonged retaining at high concentration in tumor, relatively fast clearance from normal tissue and high therapeutic efficiency of photodynamic treatment on model tumors.

Physico-chemical properties, biodistribution in animal tissues, and PDT efficacy of bacteriochlorin photosensitizers, namely cationic salts of synthetic meso-tetrakis(N-alkyl-3-pyridyl)bacteriochlorins were studied in НЕр2 cell line and in the LLC mouse model. The tested compounds showed high stability in the dark and high in vitro phototoxicity against НЕр2 cells (the half maximal inhibitory concentration LD50 in the range from 0.34±0.03 to 1.5±0.03μm). Synthetic bacteriochlorins rapidly accumulate in mouse tumor tissue with tumor-to-normal tissue fluorescence contrast ratios of 2.3-3.3, possess high PDT activity against LLC cells: inhibition of tumor growth, TGI 85.8-100%, increase in life span, ILS 105.7-129.2%, response rate, RR 50-100%. The highest PDT efficacy was found for meso-tetrakis[1-(4'-bromobutyl)-3-pyridyl]bacteriochlorin tetrabromide (IC50 0.34±0.03μm in vitro, TGI and RR 100% in vivo).

The results of multicenter prospective trial for efficacy of combined modality treatment: transurethral resection (TUR) + photodynamic therapy (PDT) with alasens for bladder cancer are represented in the article. Trials were organized by Research Institute of Organic Intermediates and Dyes and conducted according to clinical protocol approved by Ministry of Health of Russia, at the sites of leading Russian cancer clinical centers. The trial included 45 subjects with verified diagnosis of non-muscle-invasive bladder cancer. Patients underwent TUR of bladder with simultaneous PDT as anti-relapse treatment. Alasens was administered to patients as intravesicular instillation of 3% solution in volume of 50 ml with 1.5–2h exposure (prior to TUR). TUR was performed after instillation. PDT session was conducted immediately after the completion of TUR on a single occasion by means of combined local irradiation on tumor bed with diffuse irradiation on whole urinary bladder mucosa (light dose of local irradiation – 100 J/cm2, diffuse irradiation – 20 J/cm 2 ). Good tolerance of the treatment was noticed, there were no complications. Among 45 patients included in the trial, 35 (78%) completed 12 month protocol follow-up without relapse. The recurrence of bladder tumor was registered in 10 (22%) cases 6–12 months after TUR+PDT including 3 patients with recurrence 6 months after treatment, 3–9 months and 4–12 months. These patients underwent repeated TUR, whereafter their follow-up in the settings of the clinical trial was disposed. Thus, PDT with alasens after TUR allowed to decrease the recurrence rate of non-muscle-invasive bladder cancer for 1st year after treatment to 22% versus 40–80% for TUR as monotherapy according to literature data. The obtained results were comparable by efficiency with TUR combined with methods of adjuvant treatment for bladder tumors (the recurrence rates for 1-year follow-up after TUR+chemotherapy – 36–44%, after TUR+BCG – 20–59%).

Purpose of this study is testing manganese and gadolinium sulpho-phthalocyanines aqueous water solutions as contrast agents for MRI. In the fields of 0,5 and 7 Tesla T1 relaxation times were measured and acceleration factors of relaxation for water aqueous solutions of proposed substances were calculated. MRI studies were having done in the field 7 Tesla in rats with C6 glioma before and after injection of proposed substances there were obtained images and T1-cards. The dynamics of tissue contrast was monitored. The measured acceleration factors of relaxation of proposed substances are comparable to the corresponding values for Magnevist TM. Reliable reduction of T1 for 1-2 hours is marked, which leads to a significant increase in signal from the tumor on T1-weighted images. In contrast to known agents drugs based on gadolinium chelates these solutions retain stay longer in the body, which allowing for more detailed MRI studies.

The antitumor properties of pulsed laser hyperthermia (PLH) based on nanoparticles (Nps) of silver (Agks and Agkv), the phthalocyanines of aluminum (AlPc). Zinc (ZnPc), cobalt (CoPc), metal-free phthalocyanine (H2Pc) were assessed. Under the optimum conditions, PLH based on ZnPc and Agks Nps had a comparable anti-tumor effect and resulted in long-term suppression of mouse tumor S-37 growth by 100-83%. The investigations have shown that PLH based on Nps as thermosensitizers has a marked antitumor effect. The findings suggest that it is expedient to conduct further comprehensive (preclinical) studies of the antitumor therapy technique in the experiment.

Contrast agents (CA) are used to increase contrast of tumors (especially metastases) during magnetic resonance imaging (MRI). The most applied group of CA is based on coordination complexes of paramagnetic Ions, mostly Gadolinium and Manganese complexes [1]. In addition to high paramagnetic properties, efficient CA is supposed to selectively accumulate in tumor, quickly achieving its maximum content in tissue and retaining it for the duration of diagnostic procedure, while sufficiently fast (preferably in less than 24 hours) clear from the normal tissue (after the end of the procedure). The work is devoted to study of Manganese(III) chloride tetra-3-phenylthio-tetra-5-tert-buthylphthalocyanine [3-(PhS)(4)-5-(t-Bu)(4)PcMnCl] as potential CA for MRI.

The possibility of PDT application with the use of Russian photosensitizers for the brain tumors treatment is an actual problem. In this study we have shown that the drug selectively and dose-dependently accumulates in the glioblastoma 101/8 tissue. It is established that PDT should be carried out in 24 hours after the injection of Photosense on 7-th day of glioblastoma transplantation. The efficiency of PDT with a Photosense for a glioblastoma 101/8 was proved by a tumor pathomorphism. Estimated the pathomorphism 72 hours after PDT, we found the apparent damage of the tumor: necrosis and apoptosis of the tumor cells, thrombosis and destruction of the vessels with massive hemorrhage. After the PDT treatment the mitosis in the glioblastoma tissue is not determined. Thus, the possibility of PDT with a Photosense in the treatment of brain tumors is presented.

In 1992-2006 at P.A. Hertsen Moscow Oncology Research Institute photodynamic therapy (PDT) was performed in 48 esophageal cancer patients (total 48 lesions). For PDT we used Russian photosensitizers (Photogem, Photosens, Radachlorin, Alasens), Russian diode lasers (Crystall) and endoscopic equipment. As a result of PDT complete regression was in 77% of esophageal cancer lesions, partial regression was in 23%. The follow-up period was 3-11 years. Median of survival was in 4.59 years of esophageal cancer patient.

This study represents the results of clinical trial studying biologically active substance «Supreme Linchgy» as a complimentary therapy of advanced melanoma patients undergoing chemotherapy

The present review describes the history of one of the promising methods of non-invasive diagnosis of skin melanoma, dermatoscopy. The method of epiluminescent superficial skin microscopy was first applied in 1663 by Johan Christophorus Kolhaus. The history of dermatoscopy goes back to the description of the first differentially-diagnostic algorithm (Pattern analysis) as well as the invention and clinical application of manual dermatoscope. The results of examination of 90 patients with 175 skin neoplasms (including 20 melanomas) using digital photos, epiluminescent and fluorescent dermatoscopies have been presented.

Copper–nickel (CuNi) alloy nanoparticles with Curie temperatures (Tc) from 40 to 60∘C were synthesized by several techniques. Varying the synthesis parameters and post-treatment, as well as separations by size and Tc, allow producing mediator nanoparticles for magnetic fluid hyperthermia with parametric feedback temperature control with desired parameters. In vitro and in vivo animal experiments have demonstrated the feasibility of the temperature-controlled heating of the tissue, laden with the particles, by an external alternating magnetic field.

The paper describes methods for early diagnosis of cutaneous melanoma. It presents methodology and analysis of results of comprehensive dermatoscopy of 36 patients with 45 pigmented skin lesions. Sensitivity and specificity of this method in the diagnosis of melanoma were 100 and 83% respectively.

This work are devoted our experience with photodynamic therapy (PDT) with <> for patients with choroidal neovascularization (CNV). 18 patients with subfoveal CNV in age-related macular degeneration (AMD), 24 patients with subfoveal CNV in pathological myopia (PM) and 4 patients with subfoveal CNV associated with toxoplasmic retinochoroiditis were observed. CNV was 100% classic in all study patients. Standardized protocol refraction, visual acuity testing, ophthalmologic examinations, biomicroscopy, fluorescein angiography, and ultrasonography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment; were used to evaluate the results of photodynamic therapy with <> (0.02% solution of mixture sulfonated aluminium phtalocyanine 0.05 mg/kg, intravenously). A diode laser (<>, Inc, Moscow) was used operating in the range of 675 nm. Need for retreatment was based on fluorescein angiographic evidence of leakage at 3-month follow-up intervals. At 3, 6, 9 month 26 (56.5%) patients had significant improvement in the mean visual acuity. At the end of the 12-month minimal fluorescein leakage from choroidal neovascularization was seen in 12 (26.1%) patients and the mean visual acuity was slightly worse than 0.2 which was not statistically significant as compared with the baseline visual acuity. Patients with fluorescein leakage from CNV underwent repeated PDT with <>. 3D-mode ultrasound shown the decreasing thickness of chorioretinal complex in CNV area. Photodynamic therapy with <> can safely reduce the risk of severe vision loss in patients with predominantly classic subfoveal choroidal neovascularization secondary to AMD, PM and toxoplasmic retinochoroiditis.

The new aqueous gel compositions based on 5-aminolevulinic acid (ALA) for fluorescent diagnostics and photodynamic therapy of superficial diseases have been elaborated. Biodegradable polymer was used as gel-forming component and some additives - solubilizer, emulgator etc - were used to improve distribution uniformity and penetration ability. These new compositions represent colorless and transparent gels which are long-term stable at the storage temperature of ≤5°C. The effectiveness of aqueous gels as ALA delivery systems is demonstrated. After topical administration of the gel at the skin with Ehrlich tumor inoculated subcutaneously, ALA effectively induces the synthesis of protoporphyrine IX (PPIX) in the skin and in the tumor. Intensity of ALA-induced PPIX fluorescence grows with increasing ALA concentration in the gel and time of gel application. The deepness of ALA penetration in the tumor reaches 5-6 mm after 4 h gel application. A distribution of ALA-induced PPIX in mouse tumor tissue after 4 h gel application depends on ALA concentration in gel. Intensity of PPIX fluorescence in deep-located part of tumor was substantially higher with gel containing 20% ALA than with ones containing 10% or 5% ALA.

Choroidal metastasis (CM) are more and more spreading type of eye's neoplasma. The frequency of CM is increasing with prolonging of cancer patients' life. And it makes worse the quality of their life because blindness. Photodynamic therapy (PDT) is very delicate modality, which can be used for this purpose. The aim of this work was to open the possibility and to determine the efficacy of photodynamic therapy (PDT) in the treatment of patients with CM. PDT was performed simultaneously with standard chemotherapy in 8 oncological patients with CM. We used photosensitizer Photosens in doses of 0.3 mg/kg and light doses 150 J/cm2 (675 nm). PDT was performed in the some stances. Its are ranged from 7 to 10. Complete tumor regression was achieved in 6 cases. The high retina ablation was developed in one case. And in one case effect was not complete: tumor size reduced from 5 mm to 3 mm of thickness. We didn't notice any recurrence for 6-18 months follow-up. PDT is modality that could to be used in the in the combined treatment of the CM.

14 patients with transional-cell bladder cancer in stage T1N0M0G2 after transurethral bladder resection were offered adjuvant treatment with PDT. Adjuvant PDT was performed 1-1.5 months after transurethral bladder resection for superficial bladder cancer. Prior to PDT conventional and fluorescent cystoscopy were performed. In the absence of inflammation and after full epitalisation of postoperative wound a session of therapy was performed. 24 hours prior to PDT-session photosensitizer Photosens was injected intravenously in the dose of 0.8 mg per kg of body weight. Prior to PDT local anesthesia of urethra with lidocain-gel was performed. Cystoscopy was carried out. PDT was performed with diode laser "Biospec" (675 nm). During the session the place of standing diffuser and the volume of a bladder were controlled.After 7 months of observation no tumor recidivists were observed. Registered side effects were not life-threatened. 5 patients had pain or discomfort in suprapubic area, ceasing spontaneously or requiring administration of analgetics. No systemic side-effects or allergic reactions were observed. The method can be used in out-patient practice. Absence of early recidivists shows efficiency of PDT in the treatment of superficial bladder cancer. Further study is necessary to estimate optimal regimen of PDT. The further controlling of condition on the patients in this group is required.At the laboratory animals' experiment, we conducted the explorations devoted to the influence of the photodynamic effect at the prostate's tissues.