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Gamma-ray emitting 111In, which is extensively used for imaging, is also a source of short-range Auger electrons (AE). While exhibiting negligible effect outside cells, these AE become highly toxic near DNA within the cell nucleus. Therefore, these radionuclides can be used as a therapeutic anticancer agent if delivered precisely into the nuclei of tumor target cells. Modular nanotransporters (MNTs) designed to provide receptor-targeted delivery of short-range therapeutic cargoes into the nuclei of target cells are perspective candidates for specific intracellular delivery of AE emitters. The objective of this study was to evaluate the in vitro and in vivo efficacy of 111In attached MNTs to kill human bladder cancer cells overexpressing epidermal growth factor receptor (EGFR). The cytotoxicity of 111In delivered by the EGFR-targeted MNT (111In-MNT) was greatly enhanced on EJ-, HT-1376-, and 5637-expressing EGFR bladder cancer cell lines compared with 111In non-targeted control. In vivo microSPECT/CT imaging and antitumor efficacy studies revealed prolonged intratumoral retention of 111In-MNT with t½ = 4.1 ± 0.5 days as well as significant dose-dependent tumor growth delay (up to 90% growth inhibition) after local infusion of 111In-MNT in EJ xenograft-bearing mice.

Introduction.Bacteriochlorins are the most promising photosensitizers absorbing in the near-infrared spectral region. Their use can enhance the efficiency of photodynamic therapy due to the deeper penetration of radiation into the tumor.Objectiveto conduct a preclinical study of the photoinduced antitumor activity and biodistribution of Bacteriosens.Materials and methods.Bacteriosens is a preparation based on meso-tetra(3-pyridyl)bacteriochlorin absorbing at 747 nm. Photoinduced cytotoxicity was investigated in vitro using human tumor cells: A549, Hep 2, BT-474, MCF-7, SK-BR-3, PC3, and EJ and murine tumor cells: S37, C26, and LLC. In vivo studies were performed in mice with large and small tumors (S37, LLC, and C26).Results.In vitro investigation show that bacteriosens during optical irradiation led to the effective suppression of tumor cell growth in culture (the IC50 value varied from 0,08μМ to 1,21 μМ) and had no toxicity without exposure to light. The effective photodynamic therapy regimen using Bacteriosens in mice with inoculated small and large tumors of different genesis resulted in regression of a primary tumor node on 90–100 % of the animals in the absence of tumor recurrence within 90 days after treatment.Conclusion.Bacteriosens is a promising agent for the photodynamic therapy of small and large tumors; it can be successfully used as an alternative, organ-sparing minimally invasive treatment for malignant tumors, including prostate cancer.

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Introduction 1. Features of Targeted Delivery of Therapeutic Radionuclides 2. Design of Pharmaceuticals for Targeted Radionuclide Therapy (TRT) 2.1. Radionuclides 2.2. Synthesis of Radioconjugates 2.3. Targeting Carriers 4. Subcellular Targeting of Radionuclides 5. TRT Dosimetry Conclusion

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Introduction. Special attention has been recently paid to photosensitizers that absorb and fluoresce in the near infrared region of the spectrum. One of the most promising photosensitizers is bacteriosens, a synthetic bacteriochlorin derivative. Objective. To conduct a preclinical study of the biodistribution and pharmacokinetics of bacteriosens in animals.Materials and methods. The active ingredient of bacteriosens is (meso-tetra(3-pyridyl)bacteriochlorin) with of λmax 747 nm). The biodistribution and pharmacokinetics of the agent were studied in mice and rabbits. It was administered intravenously once at three doses: 1.0; 2.5 and 6.25 mg/kg for the mice and 0.236; 0.59 and 1.475 mg/kg for the rabbits. Local fluorescence spectroscopy was used for the quantitative determination of the pharmacokinetic parameters of bacteriosens.Results. Bacteriosens was removed quickly from the mouse bloodstream at 1 and 4 days after using minimal (1.0 mg/kg) and maximal (6.25 mg/kg) doses, respectively. When given at doses of 6.25 mg/kg and 1.0 mg/kg, bacteriosens was recorded in the skin, muscle, and spleen for 4 days and 24 h, respectively. The agent most intensively accumulated and long persisted in the omentum, liver, and kidneys for more than 6 days (6.25 mg/kg) and 2 days (1.0 mg/kg). A similar pattern was observed in the rabbits. Bacteriosens was rapidly removed from the rabbit bloodstream at 1 and 3 days after using at doses of 0.236 and 1.475 mg/kg, respectively. The agent was recorded in the skin, muscle, and spleen up to 4 days (1.475 mg/kg) and 3 days (0.236 mg/kg). It most intensively accumulated and long persisted in the omentum, liver, and kidneys for more than 6 days (1.475 mg/kg) and 4 days (0.236 mg/kg).Conclusion. Bacteriosens was removed from the animal bloodstream within 3–4 days after administration of the maximum dose that was 2.5 times higher than therapeutic one. The half-life of bacteriosens for mice was directly proportional to the dose and increased from 8 to 24 min; the half-life for rabbits was 20 min, irrespective of the dose. The drug was recorded in the skin for no more than 4 days. The main routes of bacteriosens elimination from the body of animals were the kidneys and liver.The study was performed in accordance with ethical principles adopted by the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes.