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1.
Theranostics ; 14(8): 3193-3212, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855185

RESUMO

As a developing radiation treatment for tumors, neutron capture therapy (NCT) has less side effects and a higher efficacy than conventional radiation therapy. Drugs with specific isotopes are indispensable counterparts of NCT, as they are the indespensable part of the neutron capture reaction. Since the creation of the first and second generations of boron-containing reagents, NCT has significantly advanced. Notwithstanding, the extant NCT medications, predominantly comprised of small molecule boron medicines, have encountered challenges such monofunctionality, inadequate targeting of tumors, and hypermetabolism. There is an urgent need to promote the research and development of new types of NCT drugs. Bio-nanomaterials can be introduced into the realm of NCT, and nanotechnology can give conventional medications richer functionality and significant adaptability. This can complement the advantages of each other and is expected to develop more new drugs with less toxicity, low side effects, better tumor targeting, and high biocompatibility. In this review, we summarized the research progress of nano-drugs in NCT based on the different types and sources of isotopes used, and introduced the attempts and efforts made by relevant researchers in combining nanomaterials with NCT, hoping to provide pivotal references for promoting the development of the field of tumor radiotherapy.


Assuntos
Neoplasias , Humanos , Neoplasias/radioterapia , Neoplasias/tratamento farmacológico , Animais , Terapia por Captura de Nêutron/métodos , Nanopartículas/química , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Nanotecnologia/métodos , Terapia por Captura de Nêutron de Boro/métodos , Compostos de Boro/uso terapêutico , Compostos de Boro/química , Compostos de Boro/farmacologia
2.
Radiol Phys Technol ; 17(1): 135-142, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37989987

RESUMO

Neutron capture therapy (NCT) with various concentrations of gadolinium (157Gd) is one of the treatment modalities for glioblastoma (GBM) tumors. Current study aims to evaluate how variations of 157Gd concentration and cell oxygen levels can affect the relative biological effectiveness (RBE) of gadolinium neutron capture therapy (GdNCT) technique through a hybrid Monte Carlo (MC) simulation approach. At first, Snyder phantom including a spherical tumor was simulated by Geant4 MC code and relevant energy electron spectra to different 157Gd concentrations including 100, 250, 500, and 1000 ppm were calculated following the neutron irradiation of simulated phantom. Scored energy electron spectra were then imported to Monte Carlo damage simulation (MCDS) code to estimate RBE values (both RBESSB and RBEDSB) at different gadolinium concentrations and oxygen levels from 10 to 100%. The results indicate that variations of 157Gd can affect the energy spectrum of released secondary electrons including Auger electrons. Variation of gadolinium concentration from 100 to 1000 ppm in tumor region can change RBESSB and RBEDSB values by about 0.1% and 0.5%, respectively. Besides, maximum variations of 4.3% and 2% were calculated for RBEDSB and RBESSB when cell oxygen level changed from 10 to 100%. From the results, variations of considered gadolinium and oxygen concentrations during GdNCT can influence RBE values. Nevertheless, due to the not remarkable changes in the intensity of Auger electrons, a slight difference in RBE values would be expected at various 157Gd concentrations, although considerable RBE changes were calculated relevant to the oxygen alternations inside tumor tissue.


Assuntos
Neoplasias Encefálicas , Terapia por Captura de Nêutron , Humanos , Gadolínio , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Terapia por Captura de Nêutron/métodos , Eficiência Biológica Relativa , Dosagem Radioterapêutica , Método de Monte Carlo
3.
Mol Pharm ; 20(12): 6311-6318, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37909734

RESUMO

Noninvasive monitoring of boron agent biodistribution is required in advance of neutron capture therapy. In this study, we developed a gadolinium-boron-conjugated albumin (Gd-MID-BSA) for MRI-guided neutron capture therapy. Gd-MID-BSA was prepared by labeling bovine serum albumin with a maleimide-functionalized gadolinium complex and a maleimide-functionalized closo-dodecaborate orthogonally. The accumulation of Gd-MID-BSA in tumors in CT26 tumor-bearing mice reached a maximum at 24 h after the injection, as confirmed by T1-based MRI and biodistribution analysis using inductively coupled plasma optical emission spectrometry. The concentrations of boron and gadolinium in the tumors exceeded the thresholds required for boron neutron capture therapy (BNCT) and gadolinium neutron capture therapy (GdNCT), respectively. The boron concentration ratios of tumor to blood and tumor to normal tissues satisfied the clinical criteria, indicating the reduction of undesired nuclear reactions of endogenous nuclei. The molar ratio of boron to gadolinium in the tumor was close to that of Gd-MID-BSA, demonstrating that the accumulation of Gd-MID-BSA in the tumor can be evaluated by MRI. Thermal neutron irradiation with Gd-MID-BSA resulted in significant suppression of tumor growth compared to the group injected with a boron-conjugated albumin without gadolinium (MID-BSA). The neutron irradiation with Gd-MID-BSA did not cause apparent side effects. These results demonstrate that the conjugation of gadolinium and boron within the albumin molecule offers a novel strategy for enhancing the therapeutic effect of BNCT and the potential of MRI-guided neutron capture therapy as a promising treatment for malignant tumors.


Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias , Terapia por Captura de Nêutron , Camundongos , Animais , Boro , Gadolínio , Distribuição Tecidual , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Neoplasias/tratamento farmacológico , Terapia por Captura de Nêutron/métodos , Imageamento por Ressonância Magnética/métodos , Terapia por Captura de Nêutron de Boro/métodos , Maleimidas
4.
JNCI Cancer Spectr ; 5(4)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34350377

RESUMO

In a time of rapid advances in science and technology, the opportunities for radiation oncology are undergoing transformational change. The linkage between and understanding of the physical dose and induced biological perturbations are opening entirely new areas of application. The ability to define anatomic extent of disease and the elucidation of the biology of metastases has brought a key role for radiation oncology for treating metastatic disease. That radiation can stimulate and suppress subpopulations of the immune response makes radiation a key participant in cancer immunotherapy. Targeted radiopharmaceutical therapy delivers radiation systemically with radionuclides and carrier molecules selected for their physical, chemical, and biochemical properties. Radiation oncology usage of "big data" and machine learning and artificial intelligence adds the opportunity to markedly change the workflow for clinical practice while physically targeting and adapting radiation fields in real time. Future precision targeting requires multidimensional understanding of the imaging, underlying biology, and anatomical relationship among tissues for radiation as spatial and temporal "focused biology." Other means of energy delivery are available as are agents that can be activated by radiation with increasing ability to target treatments. With broad applicability of radiation in cancer treatment, radiation therapy is a necessity for effective cancer care, opening a career path for global health serving the medically underserved in geographically isolated populations as a substantial societal contribution addressing health disparities. Understanding risk and mitigation of radiation injury make it an important discipline for and beyond cancer care including energy policy, space exploration, national security, and global partnerships.


Assuntos
Inteligência Artificial/tendências , Neoplasias/radioterapia , Assistência Centrada no Paciente/tendências , Radioterapia (Especialidade)/tendências , Pesquisa/tendências , Big Data , Ensaios Clínicos como Assunto , Humanos , Hipertermia Induzida , Terapia por Captura de Nêutron/métodos , Assistência Centrada no Paciente/organização & administração , Fotoquimioterapia , Radioterapia (Especialidade)/organização & administração , Tolerância a Radiação , Radiobiologia/educação , Compostos Radiofarmacêuticos/uso terapêutico , Radioterapia/efeitos adversos , Radioterapia/métodos , Radioterapia/tendências , Eficiência Biológica Relativa , Pesquisa/organização & administração , Apoio à Pesquisa como Assunto
5.
Biochem Biophys Res Commun ; 568: 23-29, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34174538

RESUMO

Gadolinium neutron capture therapy (GdNCT) is a form of binary radiotherapy. It utilizes nuclear reactions that occur when gadolinium-157 is irradiated with thermal neutrons, producing high-energy γ-rays and Auger electrons. Herein, we evaluate the potential of GdNCT for cancer treatment using PEGylated liposome incorporated with an FDA-approved MRI contrast agent. The clinical gadolinium complex (Gadovist®) was successfully encapsulated inside the aqueous core of PEGylated liposomes by repeated freeze and thaw cycling. At a concentration of 152 µM Gd, the Gd-liposome showed high cytotoxicity upon thermal-neutron irradiation. In animal experiments, when a CT26 tumor model was administered with Gd-liposomes (19 mg 157Gd per kg) followed by 20-min irradiation of thermal neutron at a flux of 1.94 × 104 cm-2 s-1, tumor growth was suppressed by 43%, compared to that in the control group, on the 23rd day of post-irradiation. After two-cycle GdNCT treatment at a 10-day interval, tumor growth was more efficiently retarded. On the 31st day after irradiation, the weight of the excised tumor in the GdNCT group (38 mg 157Gd per kg per injection) was only 30% of that of the control group. These results demonstrate the potential of GdNCT using PEGylated liposomes containing MRI contrast agents in cancer treatment.


Assuntos
Gadolínio/administração & dosagem , Isótopos/administração & dosagem , Lipossomos/química , Neoplasias/radioterapia , Terapia por Captura de Nêutron , Animais , Linhagem Celular Tumoral , Feminino , Gadolínio/uso terapêutico , Humanos , Isótopos/uso terapêutico , Camundongos Endogâmicos BALB C , Terapia por Captura de Nêutron/métodos , Polietilenoglicóis/química
6.
Appl Radiat Isot ; 164: 109270, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32819508

RESUMO

Neutron capture therapy using 157Gd (Gd-NCT) is currently under development as a cancer radiotherapy. Melanoma cells were treated with gadolinium-loaded chitosan nanoparticles (Gd-nanoCPs) for Gd-NCT. Smaller Gd-nanoCPs had higher Gd content and better cellular association of Gd and thereby made the tumor-killing effect more efficient in comparison to larger Gd-nanoCPs. This indicates that Gd-nanoCP size reduction is an efficient method for improving the cellular affinity of Gd-nanoCPs and for enhancing the tumor-killing effect of Gd-NCT.


Assuntos
Quitosana/química , Gadolínio/química , Melanoma Experimental/radioterapia , Nanopartículas/química , Terapia por Captura de Nêutron/métodos , Animais , Proliferação de Células , Melanoma Experimental/patologia , Camundongos , Peso Molecular , Tamanho da Partícula
7.
Sci Rep ; 10(1): 13417, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32770174

RESUMO

This study investigates the photon production from thermal neutron capture in a gadolinium (Gd) infused tumor as a result of secondary neutrons from particle therapy. Gadolinium contrast agents used in MRI are distributed within the tumor volume and can act as neutron capture agents. As a result of particle therapy, secondary neutrons are produced and absorbed by Gd in the tumor providing potential enhanced localized dose in addition to a signature photon spectrum that can be used to produce an image of the Gd enriched tumor. To investigate this imaging application, Monte Carlo (MC) simulations were performed for 10 different particles using a 5-10 cm spread out-Bragg peak (SOBP) centered on an 8 cm3, 3 mg/g Gd infused tumor. For a proton beam, 1.9 × 106 neutron captures per RBE weighted Gray Equivalent dose (GyE) occurred within the Gd tumor region. Antiprotons ([Formula: see text]), negative pions (- π), and helium (He) ion beams resulted in 10, 17 and 1.3 times larger Gd neutron captures per GyE than protons, respectively. Therefore, the characteristic photon based spectroscopic imaging and secondary Gd dose enhancement could be viable and likely beneficial for these three particles.


Assuntos
Gadolínio , Neoplasias/radioterapia , Terapia por Captura de Nêutron/métodos , Fótons , Humanos , Imageamento por Ressonância Magnética/métodos , Método de Monte Carlo , Neoplasias/diagnóstico por imagem , Nêutrons , Dosagem Radioterapêutica
8.
Contrast Media Mol Imaging ; 2018: 3727109, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30515066

RESUMO

Gadolinium-neutron capture therapy (Gd-NCT) is based on the nuclear capture reaction that occurs when 157Gd is irradiated with low energy thermal neutrons to primarily produce gamma photons. Herein, we investigated the effect of neutron capture therapy (NCT) using a small molecular gadolinium complex, Gd-DO3A-benzothiazole (Gd-DO3A-BTA), which could be a good candidate for use as an NCT drug due to its ability to enter the intracellular nuclei of tumor cells. Furthermore, MRI images of Gd-DO3A-BTA showed a clear signal enhancement in the tumor, and the images also played a key role in planning NCT by providing accurate information on the in vivo uptake time and duration of Gd-DO3A-BTA. We injected Gd-DO3A-BTA into MDA-MB-231 breast tumor-bearing mice and irradiated the tumors with cyclotron neutrons at the maximum accumulation time (postinjection 6 h); then, we observed the size of the growing tumor for 60 days. Gd-DO3A-BTA showed good therapeutic effects of chemo-Gd-NCT for the in vivo tumor models. Simultaneously, the Gd-DO3A-BTA groups ([Gd-DO3A-BTA(+), NCT(+)]) showed a significant reduction in tumor size (p < 0.05), and the inhibitory effect on tumor growth was exhibited in the following order: [Gd-DO3A-BTA(+), NCT(+)] > [Gd-DO3A-BTA(+), NCT(-)] > [Gd-DO3A-BTA(-), NCT(+)] > [Gd-DO3A-BTA(-), NCT(-)]. On day 60, the [Gd-DO3A-BTA(+), NCT(+)] and [Gd-DO3A-BTA(-), NCT(-)] groups exhibited an approximately 4.5-fold difference in tumor size. Immunohistochemistry studies demonstrated that new combinational therapy with chemo-Gd-NCT could treat breast cancer by both the inhibition of tumor cell proliferation and induction of apoptosis-related proteins, with in vivo tumor monitoring by MRI.


Assuntos
Benzotiazóis/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Gadolínio/uso terapêutico , Terapia por Captura de Nêutron/métodos , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Combinação de Medicamentos , Xenoenxertos , Humanos , Imageamento por Ressonância Magnética/métodos , Camundongos , Carga Tumoral/efeitos dos fármacos
9.
Appl Radiat Isot ; 130: 131-139, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28963960

RESUMO

The goal of this study was to investigate the production, purification and immobilization techniques for a 153Gd brachytherapy source. We have investigated the maximum attainable specific activity of 153Gd through the irradiation of Gd2O3 enriched to 30.6% 152Gd at McMaster Nuclear Reactor. The advantage of producing 153Gd through this production pathway is the possibility to irradiate pre-sealed pellets of 152Gd enriched Gd2O3, thereby removing the need to perform chemical separation with large quantities of radio-impurities. However, small amounts of long-lived impurities are produced from the irradiation of enriched 152Gd targets due to traces of Eu in the sample. If the amount of impurities produced is deemed unacceptable, 153Gd can be isolated as an aqueous solution, chemically separated from impurities and loaded onto a sorbent with a high affinity for Gd before encapsulation.


Assuntos
Braquiterapia/métodos , Gadolínio/uso terapêutico , Terapia por Captura de Nêutron/métodos , Radioisótopos/uso terapêutico , Gadolínio/isolamento & purificação , Humanos , Reatores Nucleares , Radioisótopos/isolamento & purificação , Dosagem Radioterapêutica
10.
Future Med Chem ; 8(8): 899-917, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27195428

RESUMO

Gadolinium neutron capture therapy (Gd-NCT) is currently under development as an alternative approach for cancer therapy. All of the clinical experience to date with NCT is done with (10)B, known as boron neutron capture therapy (BNCT), a binary treatment combining neutron irradiation with the delivery of boron-containing compounds to tumors. Currently, the use of Gd for NCT has been getting more attention because of its highest neutron cross-section. Although Gd-NCT was first proposed many years ago, its development has suffered due to lack of appropriate tumor-selective Gd agents. This review aims to highlight the recent advances for the design, synthesis and biological testing of new Gd- and B-Gd-containing compounds with the task of finding the best systems able to improve the NCT clinical outcome.


Assuntos
Boro/uso terapêutico , Gadolínio/uso terapêutico , Neoplasias/radioterapia , Terapia por Captura de Nêutron/métodos , Boro/farmacocinética , Gadolínio/farmacocinética , Humanos
11.
Appl Radiat Isot ; 117: 27-31, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27102306

RESUMO

Regardless the motivation terrorism is the most important risk for the national security in many countries. Attacks with explosives are the most common method used by terrorists. Therefore several procedures to detect explosives are utilized; among these methods are the use of neutrons and photons. In this study the Monte Carlo method an explosive detection system using a 241AmBe neutron source was designed. In the design light water, paraffin, polyethylene, and graphite were used as moderators. In the work the explosive RDX was used and the induced gamma rays due to neutron capture in the explosive was estimated using NaI(Tl) and HPGe detectors. When light water is used as moderator and HPGe as the detector the system has the best performance allowing distinguishing between the explosive and urea. For the final design the Ambient dose equivalent for neutrons and photons were estimated along the radial and axial axis.


Assuntos
Amerício/análise , Substâncias Explosivas/análise , Substâncias Explosivas/química , Método de Monte Carlo , Terapia por Captura de Nêutron/instrumentação , Espectrometria gama/instrumentação , Amerício/química , Simulação por Computador , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Modelos Estatísticos , Terapia por Captura de Nêutron/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria gama/métodos
12.
J Cancer Res Clin Oncol ; 142(4): 767-75, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26650198

RESUMO

PURPOSE: A more immediate impact for therapeutic approaches of current clinical research efforts is of major interest, which might be obtained by developing a noninvasive radiation dose-escalation strategy, and neutron capture therapy represents one such novel approach. Furthermore, some recent researches on neutron capture therapy have focused on using gadolinium as an alternative or complementary for currently used boron, taking into account several advantages that gadolinium offers. Therefore, in this study, we carried out feasibility evaluation for both single and multiple injections of gadolinium-based MRI contrast agent incorporated in calcium phosphate nanoparticles as neutron capture therapy agent. METHODS: In vivo evaluation was performed on colon carcinoma Col-26 tumor-bearing mice irradiated at nuclear reactor facility of Kyoto University Research Reactor Institute with average neutron fluence of 1.8 × 10(12) n/cm(2). Antitumor effectivity was evaluated based on tumor growth suppression assessed until 27 days after neutron irradiation, followed by histopathological analysis on tumor slice. RESULTS: The experimental results showed that the tumor growth of irradiated mice injected beforehand with Gd-DTPA-incorporating calcium phosphate-based nanoparticles was suppressed up to four times higher compared to the non-treated group, supported by the results of histopathological analysis. CONCLUSION: The results of antitumor effectivity observed on tumor-bearing mice after neutron irradiation indicated possible effectivity of gadolinium-based neutron capture therapy treatment.


Assuntos
Fosfatos de Cálcio/administração & dosagem , Neoplasias do Colo/patologia , Neoplasias do Colo/radioterapia , Meios de Contraste/administração & dosagem , Gadolínio DTPA/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Nanopartículas/administração & dosagem , Terapia por Captura de Nêutron/métodos , Animais , Estudos de Viabilidade , Feminino , Humanos , Injeções , Japão , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/radioterapia , Dosagem Radioterapêutica , Distribuição Tecidual , Resultado do Tratamento
13.
J Natl Compr Canc Netw ; 13(7): 847-55; quiz 856, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26150579

RESUMO

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Carbono/uso terapêutico , Guias como Assunto , Radioterapia com Íons Pesados/métodos , Humanos , Terapia por Captura de Nêutron/métodos , Terapia com Prótons/métodos
14.
Australas Phys Eng Sci Med ; 37(3): 541-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24961208

RESUMO

The aim of this study is to compare dose enhancement of various agents, nanoparticles and chemotherapy drugs for neutron capture therapy. A (252)Cf source was simulated to obtain its dosimetric parameters, including air kerma strength, dose rate constant, radial dose function and total dose rates. These results were compared with previously published data. Using (252)Cf as a neutron source, the in-tumour dose enhancements in the presence of atomic (10)B, (157)Gd and (33)S agents; (10)B, (157)Gd, (33)S nanoparticles; and Bortezomib and Amifostine chemotherapy drugs were calculated and compared in neutron capture therapy. Monte Carlo code MCNPX was used for simulation of the (252)Cf source, a soft tissue phantom, and a tumour containing each capture agent. Dose enhancement for 100, 200 and 500 ppm of the mentioned media was calculated. Calculated dosimetric parameters of the (252)Cf source were in agreement with previously published values. In comparison to other agents, maximum dose enhancement factor was obtained for 500 ppm of atomic (10)B agent and (10)B nanoparticles, equal to 1.06 and 1.08, respectively. Additionally, Bortezomib showed a considerable dose enhancement level. From a dose enhancement point of view, media containing (10)B are the best agents in neutron capture therapy. Bortezomib is a chemotherapy drug containing boron and can be proposed as an agent in boron neutron capture therapy. However, it should be noted that other physical, chemical and medical criteria should be considered in comparing the mentioned agents before their clinical use in neutron capture therapy.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Terapia por Captura de Nêutron/métodos , Dosagem Radioterapêutica , Relação Dose-Resposta à Radiação , Humanos
15.
J Nucl Med ; 55(4): 616-21, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24525207

RESUMO

UNLABELLED: Boronophenylalanine has been applied in clinical boron neutron capture therapy for the treatment of high-grade gliomas. The purpose of this study was to evaluate the pharmacokinetics of 4-borono-2-(18)F-fluoro-L-phenylalanine-fructose ((18)F-FBPA-Fr) in F98 glioma-bearing Fischer 344 rats by means of intravenous injection of (18)F-FBPA-Fr both with and without blood-brain barrier disruption (BBB-D) induced by focused ultrasound (FUS). METHODS: Dynamic PET imaging of (18)F-FBPA-Fr was performed on the ninth day after tumor implantation. Blood samples were collected to obtain an arterial input function for tracer kinetic modeling. Ten animals were scanned for approximately 3 h to estimate the uptake of (18)F radioactivity with respect to time for the pharmacokinetic analysis. Rate constants were calculated by use of a 3-compartment model. RESULTS: The accumulation of (18)F-FBPA-Fr in brain tumors and the tumor-to-contralateral brain ratio were significantly elevated after intravenous injection of (18)F-FBPA-Fr with BBB-D. (18)F-FBPA-Fr administration after sonication showed that the tumor-to-contralateral brain ratio for the sonicated tumors (3.5) was approximately 1.75-fold higher than that for the control tumors (2.0). Furthermore, the K1/k2 pharmacokinetic ratio after intravenous injection of (18)F-FBPA-Fr with BBB-D was significantly higher than that after intravenous injection without BBB-D. CONCLUSION: This study demonstrated that radioactivity in tumors and the tumor-to-normal brain ratio after intravenous injection of (18)F-FBPA-Fr with sonication were significantly higher than those in tumors without sonication. The K1/k2 ratio may be useful for indicating the degree of BBB-D induced by FUS. Further studies are needed to determine whether FUS may be useful for enhancing the delivery of boronophenylalanine in patients with high-grade gliomas.


Assuntos
Barreira Hematoencefálica/fisiologia , Compostos de Boro/metabolismo , Compostos de Boro/farmacocinética , Glicopeptídeos/farmacocinética , Terapia por Captura de Nêutron/métodos , Fenilalanina/análogos & derivados , Compostos Radiofarmacêuticos/farmacocinética , Ultrassom , Animais , Apoptose , Barreira Hematoencefálica/efeitos da radiação , Compostos de Boro/administração & dosagem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Sistemas de Liberação de Medicamentos , Glioma/diagnóstico por imagem , Glioma/metabolismo , Marcação In Situ das Extremidades Cortadas , Masculino , Transplante de Neoplasias , Fenilalanina/administração & dosagem , Fenilalanina/metabolismo , Tomografia por Emissão de Pósitrons , Ratos , Ratos Endogâmicos F344
16.
Biomed Pharmacother ; 67(6): 451-7, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23743325

RESUMO

Neutron capture therapy (NCT) is a promising non-invasive cancer therapy approach and some recent NCT research has focused on using compounds containing gadolinium as an alternative to currently used boron-10 considering several advantages that gadolinium offers compared to those of boron. In this study, we evaluated gadolinium-entrapped liposome compound as neutron capture therapy agent by in vivo experiment on colon-26 tumor-bearing mice. Gadolinium compound were injected intravenously via tail vein and allowed to accumulate into tumor site. Tumor samples were taken for quantitative analysis by ICP-MS at 2, 12, and 24 h after gadolinium compound injection. Highest gadolinium concentration was observed at about 2 h after gadolinium compound injection with an average of 40.3 µg/g of wet tumor tissue. We performed neutron irradiation at JRR-4 reactor facility of Japan Atomic Energy Research Institute in Tokaimura with average neutron fluence of 2×10¹² n/cm². The experimental results showed that the tumor growth suppression of gadolinium-injected irradiated group was revealed until about four times higher compared to the control group, and no significant weight loss were observed after treatment suggesting low systemic toxicity of this compound. The gadolinium-entrapped liposome will become one of the candidates for Gd delivery system on NCT.


Assuntos
Antineoplásicos/farmacologia , Gadolínio/farmacologia , Lipossomos/administração & dosagem , Neoplasias/tratamento farmacológico , Terapia por Captura de Nêutron/métodos , Animais , Boro/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Japão , Masculino , Camundongos , Camundongos Endogâmicos BALB C
17.
Int J Radiat Biol ; 88(12): 980-90, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22849307

RESUMO

PURPOSE: A comparative study of the effects of different radiation modalities on cell death was performed. MATERIALS AND METHODS: Radiation modalities included γ-rays, fast neutrons, a mixed energy neutron beam called the modified enhanced thermal neutron beam and the mixed beam including Auger electron irradiation by gadolinium neutron capture. U87 (human brain tumor cells) cell survival curve data were modeled to predict how cells died. Transmission electron microscopy (TEM) images were assembled into a morphology of cell death (MCD) database and used to determine the fraction of necrotic or autophagic cells. RESULTS: Linear energy transfer (LET) differences for the different radiation modalities were revealed by modeling. All radiation modalities induced autophagy but only fast neutrons induced significant levels of necrosis. No necrosis, above control levels, was found in cells irradiated with mixed beam irradiation including Auger electrons. The number of autophagosomes increased with increasing time after exposure to all radiation modalities indicating progression of autophagy but only cells irradiated with the mixed beam plus Auger electrons exhibited extreme autophagy. CONCLUSIONS: Mixed neutron beam irradiation plus Auger electron irradiation from gadolinium neutron capture is a moderately high LET modality that kills U87 cells without the induction of necrosis and with progression of autophagy to an extreme state.


Assuntos
Gadolínio/uso terapêutico , Glioblastoma/patologia , Terapia por Captura de Nêutron/métodos , Autofagia/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Glioblastoma/radioterapia , Humanos , Necrose/etiologia
18.
Chemistry ; 17(30): 8479-86, 2011 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-21671294

RESUMO

The upregulation of low-density lipoprotein (LDL) transporters in tumour cells has been exploited to deliver a sufficient amount of gadolinium/boron/ligand (Gd/B/L) probes for neutron capture therapy, a binary chemio-radiotherapy for cancer treatment. The Gd/B/L probe consists of a carborane unit (ten B atoms) bearing an aliphatic chain on one side (to bind LDL particles), and a Gd(III)/1,4,7,10-tetraazacyclododecane monoamide complex on the other (for detection by magnetic resonance imaging (MRI)). Up to 190 Gd/B/L probes were loaded per LDL particle. The uptake from tumour cells was initially assessed on cell cultures of human hepatoma (HepG2), murine melanoma (B16), and human glioblastoma (U87). The MRI assessment of the amount of Gd/B/L taken up by tumour cells was validated by inductively coupled plasma-mass-spectrometric measurements of the Gd and B content. Measurements were undertaken in vivo on mice bearing tumours in which B16 tumour cells were inoculated at the base of the neck. From the acquisition of magnetic resonance images, it was established that after 4-6 hours from the administration of the Gd/B/L-LDL particles (0.1 and 1 mmol kg(-1) of Gd and (10)B, respectively) the amount of boron taken up in the tumour region is above the threshold required for successful NCT treatment. After neutron irradiation, tumour growth was followed for 20 days by MRI. The group of treated mice showed markedly lower tumour growth with respect to the control group.


Assuntos
Boro/farmacologia , Proteínas de Transporte/metabolismo , Gadolínio/farmacologia , Imageamento por Ressonância Magnética , Terapia por Captura de Nêutron/métodos , Animais , Boro/química , Proteínas de Transporte/química , Linhagem Celular Tumoral , Gadolínio/química , Humanos , Melanoma Experimental , Camundongos , Estrutura Molecular , Regulação para Cima
19.
Biomaterials ; 31(32): 8419-25, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20701966

RESUMO

HeLa cells were incubated with neutron capture nuclei (boron-10 and gadolinium)-containing carbon nanoparticles, followed by irradiation of slow thermal neutron beam. Under a neutron flux of 6 x 10(11) n/cm(2) (or 10 min irradiation at a neutron flux of 1 x 10(9) n/cm(2) s), the percentages of acute cell death at 8 h after irradiation are 52, 55, and 28% for HeLa cells fed with BCo@CNPs, GdCo@CNPs, and Co@CNPs, respectively. The proliferation capability of the survived HeLa cells was also found to be significantly suppressed. At 48 h after neutron irradiation, the cell viability further decreases to 35 +/- 5% as compared to the control set receiving the same amount of neutron irradiation dose but in the absence of carbon nanoparticles. This work demonstrates "proof-of-concept" examples of neutron capture therapy using (10)B-, (157)Gd-, and (59)Co-containing carbon nanoparticles for effective destruction of cancer cells. It will also be reported the preparation and surface functionalization of boron or gadolinium doped core-shell cobalt/carbon nanoparticles (BCo@CNPs, GdCo@CNPs and Co@CNPs) using a modified DC pulsed arc discharge method, and their characterization by various spectroscopic measurements, including TEM, XRD, SQUID, FT-IR, etc. Tumor cell targeting ability was introduced by surface modification of these carbon nanoparticles with folate moieties.


Assuntos
Boro/uso terapêutico , Cobalto/uso terapêutico , Gadolínio/uso terapêutico , Nanopartículas/química , Neoplasias/radioterapia , Terapia por Captura de Nêutron/métodos , Boro/administração & dosagem , Terapia por Captura de Nêutron de Boro/métodos , Carbono/química , Sobrevivência Celular/efeitos da radiação , Cobalto/administração & dosagem , Gadolínio/administração & dosagem , Células HeLa , Humanos , Isótopos/administração & dosagem , Isótopos/uso terapêutico , Nanopartículas/ultraestrutura
20.
Appl Radiat Isot ; 68(4-5): 643-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20096595

RESUMO

In 2002, an innovative neutron time-of-flight facility started operation at CERN: n_TOF. The main characteristics that make the new facility unique are the high instantaneous neutron flux, high resolution and wide energy range. Combined with state-of-the-art detectors and data acquisition system, these features have allowed to collect high accuracy neutron cross-section data on a variety of isotopes, many of which radioactive, of interest for Nuclear Astrophysics and for applications to advanced reactor technologies. A review of the most important results on capture and fission reactions obtained so far at n_TOF is presented, together with plans for new measurements related to nuclear industry.


Assuntos
Terapia por Captura de Nêutron/instrumentação , Terapia por Captura de Nêutron/métodos , Reatores Nucleares , Desenho de Equipamento , Análise de Falha de Equipamento , Nêutrons , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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