RESUMO
BACKGROUND: In patients with hemophilia, radionuclide synoviorthesis, or the intra-articular injection of a radionuclide to decrease the synovial hypertrophy tissue, aims to decrease or avoid hemarthrosis. AIM: To evaluate the effectiveness of radionuclide synoviorthesis in hemophilia. MATERIAL AND METHODS: Observational retrospective study of the evolution of 107 male patients aged 3 to 54 years who were subjected to radionuclide synoviorthesis between 2007 and 2015. RESULTS: Of 164 treated joints, in 65% treatment was successful, (defined as zero to two hemarthroses and absence of synovitis during the follow up period), in 17% it was partially successful (defined as two or less hemarthroses, but persistence of the synovitis) and failed in 18% of the procedures. No important complications were recorded. CONCLUSIONS: Radionuclide synoviorthesis has an overall 82% success rate, is minimally invasive, can be used at any age and is inexpensive We recommend its implementation in Chilean hemophilia treatment centers.
Assuntos
Hemartrose/terapia , Hemofilia A/terapia , Radioisótopos/administração & dosagem , Rênio/uso terapêutico , Sinovite/terapia , Radioisótopos de Ítrio/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Hemartrose/diagnóstico por imagem , Hemartrose/fisiopatologia , Hemofilia A/fisiopatologia , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sinovite/diagnóstico por imagem , Sinovite/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Background: In patients with hemophilia, radionuclide synoviorthesis, or the intra-articular injection of a radionuclide to decrease the synovial hypertrophy tissue, aims to decrease or avoid hemarthrosis. Aim: To evaluate the effectiveness of radionuclide synoviorthesis in hemophilia. Material and Methods: Observational retrospective study of the evolution of 107 male patients aged 3 to 54 years who were subjected to radionuclide synoviorthesis between 2007 and 2015. Results: Of 164 treated joints, in 65% treatment was successful, (defined as zero to two hemarthroses and absence of synovitis during the follow up period), in 17% it was partially successful (defined as two or less hemarthroses, but persistence of the synovitis) and failed in 18% of the procedures. No important complications were recorded. Conclusions: Radionuclide synoviorthesis has an overall 82% success rate, is minimally invasive, can be used at any age and is inexpensive We recommend its implementation in Chilean hemophilia treatment centers.
Assuntos
Humanos , Masculino , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Radioisótopos/administração & dosagem , Rênio/uso terapêutico , Sinovite/terapia , Radioisótopos de Ítrio/uso terapêutico , Hemartrose/terapia , Hemofilia A/terapia , Sinovite/fisiopatologia , Sinovite/diagnóstico por imagem , Fatores de Tempo , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento , Hemartrose/fisiopatologia , Hemartrose/diagnóstico por imagem , Hemofilia A/fisiopatologia , Injeções Intra-ArticularesRESUMO
Radiosynovectomy is a local form of radiotherapy used as second-line treatment in the management of inflammatory and non-inflammatory arthropathies with unsatisfactory response to local or systemic corticosteroid therapy. Its efficacy is similar to that of surgical synovectomy, with the advantages of being a low-cost and minimally- invasive treatment that requires a shorter recovery time. Its efficacy is greater in the treatment of inflammatory arthritis characterized by synovitis, such as rheumatoid arthritis and juvenile chronic arthritis with mono/oligoarticular involvement, especially in upper extremity joints. A number of isotopes can be used in colloidal suspensions. Rhenium-186-sulphide colloid is currently indicated for the treatment of medium-sized joints. The ultrasound-guided injection is suitable for small joints, such as wrist. For proper and safe use and administration of this technique the collaboration of a trained and experienced radiologist is critical to successful treatment.
La radiosinovectomía es una forma local de radioterapia utilizada como tratamiento de segunda línea en el manejo de artropatías inflamatorias y no inflamatorias con respuesta insatisfactoria a la terapia sistémica o local con corticoesteroides. Tiene una eficacia similar a la sinovectomía quirúrgica, con las ventajas de ser un tratamiento de menor costo, menos cruento y con menor tiempo de convalecencia. Su eficacia es mayor en artropatías inflamatorias caracterizadas por sinovitis, como la artritis reumatoide y artritis crónica juvenil, con compromiso mono u oligoarticular y en articulaciones de extremidades superiores. Existen múltiples isótopos que se pueden utilizar en suspensiones coloidales, siendo el sulfuro coloidal de renio-186 el utilizado para la articulación radiocarpiana. Una técnica de administración adecuada es fundamental para el éxito del tratamiento, siendo la inyección con guía ultrasonográfica adecuada para articulaciones de volumen pequeño, instancia en la que la colaboración del médico radiólogo entrenado es fundamental.
Assuntos
Feminino , Artrite Juvenil/terapia , Rênio/uso terapêutico , Sinovite/terapia , Ultrassom/métodos , Artrite Juvenil/complicações , Injeções Intra-Articulares , Punho , Compostos Radiofarmacêuticos/uso terapêutico , Seleção de Pacientes , Sinovite/etiologia , Terapia CombinadaRESUMO
The main objective of this paper was to obtain the absorbed dose profiles for radionuclides of frequent or potential use in radiosynoviortheses. These profiles reveal the absorbed dose per activity of injected radionuclide (Gy/h*MBq) in the synovial membrane and the articular cartilage. The researched radionuclides were (32)P, (90)Y, (188)Re, (177)Lu, (153)Sm and (169)Er. The therapeutic range of each radionuclides in synovial tissue were also calculated. This range determines the synovial thickness that can be sufficiently irradiated and thus successfully treated. The S values for the synovial membrane and articular cartilage were calculated using as a model a cylinder with the source uniformly distributed in its volume. The synovial membrane was simulated varying the radius of the cylinder (from 0.5cm to 9cm) and its height (from 0.01cm to 0.04cm). The area in the base of the cylinder represents different sizes of the synovial surface (small, medium and large joints). The height of the cylinder represents different stages of the progression of the rheumatoid arthritis. The same model was used to simulate the articular cartilage but, the source was uniformly distributed into a cylindrical slab (0.01cm height and 1cm of radius. The results obtained allow the estimation of the dose that will be delivered to the synovial membrane and the articular cartilage for different joint sizes and different stages of progression of the rheumatoid arthritis (RA).
Assuntos
Artrite Reumatoide/radioterapia , Manequins , Radioisótopos/farmacocinética , Radiometria/métodos , Compostos Radiofarmacêuticos/farmacocinética , Absorção , Algoritmos , Artrite Reumatoide/metabolismo , Partículas beta/uso terapêutico , Cartilagem Articular/metabolismo , Cartilagem Articular/efeitos da radiação , Érbio/farmacocinética , Érbio/uso terapêutico , Raios gama/uso terapêutico , Humanos , Lutécio/farmacocinética , Lutécio/uso terapêutico , Método de Monte Carlo , Radioisótopos de Fósforo/farmacocinética , Radioisótopos de Fósforo/uso terapêutico , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Dosagem Radioterapêutica , Rênio/farmacocinética , Rênio/uso terapêutico , Samário/farmacocinética , Samário/uso terapêutico , Membrana Sinovial/metabolismo , Membrana Sinovial/efeitos da radiação , Radioisótopos de Ítrio/farmacocinética , Radioisótopos de Ítrio/uso terapêuticoRESUMO
A multicenter study was sponsored by the International Atomic Energy Agency (IAEA) to assess the safety and efficacy of transarterial rhenium-188 ((188)Re) HDD lipiodol (radioconjugate to lipiodol using an HDD kit) in the treatment of unresectable hepatocellular carcinoma. During 5 years, 185 patients received at least 1 treatment of radioconjugate, and 51 were retreated. The level of radioconjugate administered was based on radiation-absorbed dose to critical normal organs, calculated after a "scout" dose of radioconjugate. The total injected activity, including the scout dose during the first treatment, ranged from 21 to 364 mCi (mean, 108 mCi/4 GBq). Immediate and late side-effects were minimal. Tumor size could be evaluated in 88 patients. Among these patients, the objective response rate was 25%; stable disease was observed in 53% and tumor progression in 22%. With a median follow-up of 455 days, the estimated 12- and 24-month overall survival was 46% and 23%. This multicenter study shows that (188)Re lipiodol is a safe and cost-effective method to treat primary hepatocellular carcinoma via the transarterial route and requires further evaluation by treatment of greater numbers of patients.
Assuntos
Carcinoma Hepatocelular/radioterapia , Óleo Iodado/administração & dosagem , Neoplasias Hepáticas/radioterapia , Radioisótopos/administração & dosagem , Rênio/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Intra-Arteriais , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Energia Nuclear , Prognóstico , Radioisótopos/uso terapêutico , Planejamento da Radioterapia Assistida por Computador , Rênio/uso terapêuticoRESUMO
Radioimmunotherapy (RIT) may improve the management of malignant gliomas. A Phase I clinical trial was performed to evaluate, for the first time, the toxicity and clinical effect of an intracavitary administration of a single dose of Nimotuzumab (h-R3) labeled wit (188)Re. Nimotuzumab is a humanized monoclonal antibody directed against epidermal growth factor receptors. Three patients with anaplastic astrocytoma (AA) and 8 with glioblastoma multiforme (GBM) were intended to be treated with 3 mg of mAb labelled with 10 or 15 mCi of (188)Re. In patients treated with 10 mCi (n=6) transitory worsening of pre-existing neurological symptoms were observed. Two patients treated with 15 mCi (n=4) developed early severe neurological symptoms and one also developed late severe toxicity (radionecrosis). In the group treated with 10 mCi, 1 GBM patient died in progression 6 months after the treatment, 2 patients (1 GBM and 1 AA) developed stable disease during 3 months. One GBM patient had partial response for more than 1 year and 2 patients (1 GBM and 1 AA) were asymptomatic and in complete response after 3 years of treatment. Maximal tolerated dose of the radioimmunoconjugate (188)Re-Nimotuzumab was 3 mg of the h-R3 labelled with 10 mCi of (188)Re. The radioimmunoconjugate showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5 % of the injected dose one hour post-administration. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas.
Assuntos
Anticorpos Monoclonais/toxicidade , Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Radioimunoterapia/métodos , Rênio/efeitos adversos , Adulto , Idoso , Anticorpos Monoclonais/farmacocinética , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Radioimunoterapia/efeitos adversos , Radioisótopos/efeitos adversos , Radioisótopos/uso terapêutico , Rênio/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the biodistribution, internal radiation dosimetry and safety of the 188Re-labelled humanized monoclonal antibody nimotuzumab in the locoregional treatment of malignant gliomas. METHODS: Single doses of 370 or 555 MBq of 188Re-labelled nimotuzumab were locoregionally administered to nine patients with recurrent high-grade gliomas, according to an approved dose-escalation study. SPECT, planar scintigraphy and magnetic resonance images were combined for dosimetric and pharmacokinetic studies. Blood and urine samples were collected to evaluate clinical laboratory parameters and for absorbed doses calculations. Biodistribution, internal dosimetry, human anti-mouse antibody response and toxicity were evaluated and reported. RESULTS: The 188Re-nimotuzumab showed a high retention in the surgically created resection cavity with a mean value of 85.5+/-10.3%ID 1 h post-injection. It produced mean absorbed doses in the tumour region of approximately 24.1+/-2.9 Gy in group I (patients receiving 370 MBq) and 31.1+/-6.4 Gy in group II (patients receiving 555 MBq); the normal organs receiving the highest absorbed doses were the kidneys, liver and urinary bladder. About 6.2+/-0.8%ID was excreted by the urinary pathway. The maximum tolerated dose was 370 MBq because two patients showed severe adverse effects after they received 555 MBq of 188Re-nimotuzumab. No patient developed human anti-mouse antibody response. CONCLUSIONS: A locoregional single dose of 188Re-labelled nimotuzumab of approximately 370 MBq could be used safely in the routine treatment of patients suffering with high-grade gliomas. The efficacy of this therapy needs to be evaluated in a phase II clinical trial.
Assuntos
Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/toxicidade , Carga Corporal (Radioterapia) , Glioma/metabolismo , Radioisótopos/farmacocinética , Radioisótopos/toxicidade , Rênio/farmacocinética , Rênio/toxicidade , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Relação Dose-Resposta à Radiação , Feminino , Glioma/patologia , Glioma/radioterapia , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Especificidade de Órgãos , Doses de Radiação , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/uso terapêutico , Compostos Radiofarmacêuticos/toxicidade , Rênio/uso terapêutico , Distribuição TecidualRESUMO
La restenosis luego de una angioplastia transluminal coronaria exitosa es uno de los problemas más preocupantes en el área de la cardiología intervencionista. Uno de los métodos que se han desarrollado para la prevención y el tratamiento de esta restenosis es la radiación intracoronaria. Se reporta el primer caso tratado en Uruguay con radiación intracoronaria mediante la aplicación de un balón con 188Re. Entre las ventajas que tendría este método sobre otros de radiación intracoronaria se destacan su bajo costo y la facilidad de su aplicación, sin requerir dispositivos costosos ni infraestructura sofisticada de radioprotección. La experiencia acumulada con esta nueva técnica muestra que es un procedimiento factible y seguro. Debe aguardarse más información acerca de la eficacia del mismo en la evolución alejada (AU)
Assuntos
INFORME DE CASO , Humanos , Feminino , Idoso , Rênio/uso terapêutico , Radioisótopos/uso terapêutico , Doença das Coronárias/prevenção & controle , Angioplastia Coronária com BalãoRESUMO
One of the best procedures to prevent haem-arthrosis has been radioactive synovectomy (synoviorthesis). Since the first report of radioactive synovectomy in haemophilia of Ahlberg in 1971 [1], many centres adopted this procedure as the one of choice, through fibrosing the synovial membrane, prevent further haemarthrosis. Since 1976 we have performed 104 such radioactive synoviorthesis in 97 patients, age ranging from 6 to 40 years with a mean of 10 years. Sixty-five of these patients were under 12 years of age. The knees were injected in 61 cases, elbow in 26 cases, ankles in 14 cases and shoulders in three cases. The clinical results of this procedure show 80% of excellent results with no further bleeding. In case of failure, a new injection can be given in the same joint at a 6-month interval, or an injection for the same purpose in other joint. One of the criticisms against this method is the possible chromosomal damage induced by the radioactive material. In our centre, four studies have been carried out in order to see whether these changes, when they occur, are everlasting; all have demonstrated that chromosomal changes are reversible. The radioactive material used in the two first studies was Gold-189 (189Au). In 1978, 354 metaphases were studied with 61 ruptures, 17.23% (nonpremalign) and six structural changes, considered premalign (1.69%). Any number below 2% is considered not to be dangerous. A further study was done in 1982, in the same group of patients with a result of 21 ruptures (3.34%) and no structural changes. This demonstrated that the possible premalign changes disappeared with time. A third study was performed in a series of 13 patients that sustained radioactive synoviorthesis with Rhenium-186 (186Re) in November 1991. For comparison, we carried out a chromosomal study just before and 6 months after the radioactive material injection. The results confirmed that changes that could be linked to the radiation, appeared equally in nonirradiated patients, and those changes due to the radiation disappear with time, never reaching the dangerous zone of 2%. In the group treated with 186Re we studied an additional number of 130 metaphases with identical results and no structural changes. In a study on patients where 90Y was the radiocolloid, no premalign change was found before or after the synoviorthesis. It seems, in view of these results, that radioactive synovectomy is safe and gives great benefits to the haemophilic patients.
Assuntos
Hemofilia A/complicações , Radioisótopos/administração & dosagem , Radioisótopos/toxicidade , Sinovite/tratamento farmacológico , Adolescente , Adulto , Criança , Aberrações Cromossômicas/efeitos da radiação , Análise Citogenética , Seguimentos , Radioisótopos de Ouro/administração & dosagem , Radioisótopos de Ouro/uso terapêutico , Radioisótopos de Ouro/toxicidade , Hemartrose/complicações , Hemartrose/tratamento farmacológico , Hemartrose/etiologia , Hemofilia A/patologia , Hemofilia A/terapia , Humanos , Injeções Intra-Articulares , Radioisótopos/uso terapêutico , Rênio/administração & dosagem , Rênio/uso terapêutico , Rênio/toxicidade , Segurança , Sinovite/etiologia , Sinovite/patologia , Resultado do Tratamento , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/uso terapêutico , Radioisótopos de Ítrio/toxicidadeRESUMO
188Re is one of the radioisotopes expected to emerge as useful for therapy. Development of new radiopharmaceuticals based on 188Re depends on the radiolabeling methods used, which would give stable complexes having predefined radiochemical properties and in vitro and in vivo stability. This paper has attempted to provide a perspective of 188Re-labeled monoclonal antibodies, their radiolabeling characteristics, methods for quality control of radioimmunoconjugates and in vitro stability for radioimmunotherapy of solid tumors. The direct method of 188Re radiolabeling of antibodies by reductive attachment of 188Re in which free sulfhydryl groups have been generated by reduction of the intramolecular S-S disulfide bonds has been shown to be a promising approach in particular. Moreover, excellent methods have been developed to test the radionuclide, radiochemical purity and stability of 188Re-radioimmunoconjugates using high performance liquid chromatography (HPLC) and paper chromatography.