ABSTRACT
Proton therapy can treat tumors located in radiation-sensitive tissues. This article demonstrates the possibility of enhancing the proton therapy with targeted gold nanoparticles that selectively recognize tumor cells. Au-PEG nanoparticles at concentrations above 25 mg/L and 4 Gy proton dose caused complete death of EMT6/P cells in vitro. Binary proton therapy using targeted Au-PEG-FA nanoparticles caused an 80% tumor growth inhibition effect in vivo. The use of targeted gold nanoparticles is promising for enhancing the proton irradiation effect on tumor cells and requires further research to increase the therapeutic index of the approach.
Subject(s)
Carcinoma, Ehrlich Tumor , Gold , Metal Nanoparticles , Proton Therapy , Gold/chemistry , Gold/pharmacology , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Proton Therapy/methods , Animals , Carcinoma, Ehrlich Tumor/radiotherapy , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/pathology , Mice , Cell Line, Tumor , Polyethylene Glycols/chemistryABSTRACT
Biodistribution of [125I]Aimpila (20 mg/kg) in the tumor and normal tissues, including the mammary gland tissue, after single oral dose was studied in BALB/c nude mice with T47D/ReCAF+++ human breast tumor sensitive to this drug and in closely related BALB/c nude+mice without tumors. The maximum concentration of [125I]Aimpila was in fact the same in the tumor and in the mammary gland, while the time course of its accumulation/elimination differed. The time of the maximum accumulation of the drug in the tumor was shorter and its persistence longer than in normal tissue. After 24 h, label concentration in the tumor was 4.5 times higher (p=0.002). Differences in the time course of label accumulation in the tumor were detected. The maximum ratio of tumor/blood concentrations of the preparation was recorded in 1 h after administration. [125I]Aimpila and [125I]alpha-fetoprotein accumulated in the tumor in comparable concentrations and were eliminated simultaneously at the same rate. The results of comparative analysis of accumulation of the labeled compounds in Aimpila-sensitive T47D/RECAF+++ tumor from 0.5 to 9.0 h after drug administration could be interpreted as a result of possible receptor-mediated binding of the complex with the tumor at the expense of the alpha-fetoprotein transporting part. Differences in the parameters of [125I]Aimpila biodistribution in the tumor and normal mammary tissue indirectly attested to selective antiproliferative activity of the complex.
Subject(s)
Antineoplastic Agents/pharmacokinetics , Atractyloside/pharmacokinetics , Breast Neoplasms/drug therapy , Iodine Radioisotopes/pharmacokinetics , Radiopharmaceuticals/pharmacokinetics , alpha-Fetoproteins/pharmacokinetics , Animals , Antineoplastic Agents/blood , Atractyloside/blood , Biological Availability , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Gastric Mucosa/metabolism , Humans , Iodine Radioisotopes/blood , Jejunum/metabolism , Liver/metabolism , Mammary Glands, Animal/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , Radiopharmaceuticals/blood , Swine , Tissue Distribution , Xenograft Model Antitumor Assays , alpha-Fetoproteins/metabolismABSTRACT
We studied the possibility of using BSA-coated magnetic iron oxide nanoparticles for magnetic resonance imaging diagnosis of C6 glioblastoma, 4T1 mammary adenocarcinoma, and RS-1 hepatic mucous carcinoma. In all three cases, magnetic nanoparticles accumulated in the tumor and its large vessels. Magnetic resonance imaging with contrast agent allows visualization of the tumor tissue and its vascularization.
Subject(s)
Adenocarcinoma, Mucinous/diagnostic imaging , Adenocarcinoma/diagnostic imaging , Brain Neoplasms/diagnostic imaging , Contrast Media/pharmacokinetics , Glioma/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Magnetite Nanoparticles/administration & dosage , Mammary Neoplasms, Experimental/diagnostic imaging , Adenocarcinoma/metabolism , Adenocarcinoma, Mucinous/metabolism , Animals , Brain Neoplasms/metabolism , Cell Line, Tumor , Contrast Media/chemistry , Female , Ferric Compounds/administration & dosage , Ferric Compounds/chemistry , Glioma/metabolism , Injections, Subcutaneous , Liver Neoplasms/metabolism , Magnetic Resonance Imaging/methods , Mammary Neoplasms, Experimental/metabolism , Mice , Mice, Inbred BALB C , Rats , Rats, WistarABSTRACT
In this report the efficacy of extracellular pharmaceutical Gd-DTPA in Binary Radiotherapy was studied. The study was carried out in mice bearing transplantable adenocarcinoma Ca755 using X-ray based contrast enhanced radiotherapy as a practical implementation of Binary Radiotherapy. It was shown that intravenous administration of 0.3 ml of 0.5 M water solution of Gd-DTPA followed by X-irradiation at a dose of 10 Gy provides T/C%=10±3% and leads to complete tumor regression in 25% of mice.
Subject(s)
Adenocarcinoma/radiotherapy , Gadolinium DTPA/therapeutic use , Adenocarcinoma/pathology , Animals , Female , Magnetic Resonance Imaging , Mice , Mice, Inbred C57BL , Xenograft Model Antitumor AssaysABSTRACT
The purpose of the work was to build a prompt gamma neutron activation analysis (PGNAA) facility at the MEPhI reactor for analyzing the content of various elements for NCT. The facility was implemented on a monochromatic neutron beam. Methods of quantitative (10)B and Gd measurement have been developed for pharmacokinetic studies. The facility is capable of measuring 1 microg of (10)B and 10 microg of Gd in biological samples with an error less than 10%. The detection limit of the facility is 0.3 microg of (10)B and 2 microg of Gd. Neutron flux attenuation within biological tissue samples was estimated and a new system for determining the elemental concentration was suggested.
