RESUMO
Nanomedicine is a highly demanded discipline. Liposomes have seen an increased attention due to their physicochemical properties that allow them to act as nanocarriers of drugs and also of radioisotopes that can be used to diagnose and treat cancer. In order to obtain a novel permeability cancer imaging agent based on 99mTc-labeled liposomes, we describe microwave-assisted synthesis of stearyl 6-(benzylidenehydrazinyl) nicotinamide lipid, which was included in two formulations: nanometric hydrazinonicotinic acid (HYNIC) liposome and its PEGylated coated analogue, HYNIC-PEG liposome. Radiolabeling with 99mTc via stearyl 6-(benzylidenehydrazinyl) nicotinamide was found to be easy, reproducible, and stable, revealing high radiochemical purity (94 ± 1.7%) for both liposomal formulations. Biodistribution at 4 h and 24 h and scintigraphic images at 4 h were performed in normal and melanoma-bearing C57BL/6 mice. Biodistribution studies at 4 h showed tumor uptake of 99mTc-HYNIC liposome and 99mTc-HYNIC-PEG liposome (1.1 ± 0.6 and 2.5 ± 0.4, respectively) and also at 24 h p.i. (1.8 ± 0.5 and 3.0 ± 1.1, respectively). Scintigraphic images showed appreciable tumor uptake in melanoma tumor-bearing mice with both liposomal formulations. Our results show that 99mTc stearyl 6-(benzylidenehydrazinyl) nicotinamide liposomes can be used as diagnostic noninvasive in vivo tumor-targeting agents capable of evaluating tumor permeability and development who can be used in personalized chemotherapy planning.
Assuntos
Melanoma Experimental/metabolismo , Niacinamida/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Tecnécio/farmacocinética , Animais , Linhagem Celular Tumoral , Lipossomos , Melanoma Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Niacinamida/administração & dosagem , Niacinamida/química , Permeabilidade/efeitos dos fármacos , Cintilografia/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/química , Tecnécio/administração & dosagem , Tecnécio/química , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologiaRESUMO
The aim of this work was to develop and evaluate a 99m Tc-labeled neuropeptide Y derivative with affinity toward Y1-receptor. The selected amino acid sequence included nine amino acids derived from the C-terminal portion of the NPY complemented with the addition of one cysteine-mercaptoacetic acid moiety to bind the radiometal. Labeling was achieved through the preparation of a 3 + 1 nitrido complex. Physicochemical evaluation, cell uptake, internalization and externalization studies, and competitive assays were performed. Biodistribution experiments were carried out in normal and tumor-bearing mice. A single product with radiochemical purity >90% and high stability was obtained. In vitro analysis showed specific cellular uptake, IC50 of 73.2 nM, and a high internalization rate (80%). Biodistribution studies showed low blood and renal uptake and combined hepatobiliary and urinary elimination. Preliminary studies in mice bearing induced breast tumors rendered promising uptake values.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neuropeptídeo Y/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Tecnécio/administração & dosagem , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição TecidualRESUMO
It has been suggested that technetium-99m (99mTc)-anti-tumour necrosis factor alpha (TNF-α) scintigraphy (SCI) may be a useful diagnostic tool in Graves' ophthalmopathy (GO). This study evaluated whether orbit total radioactivity uptake on SCI could be used to predict corticosteroid therapy (CorT) responses in active-GO patients. A longitudinal study of patients with active GO defined by Clinical Active Score (CAS) >3/7 was done. Clinical, laboratory and SCI evaluations were performed at baseline and 3 months after concluding intravenous CorT. SCI (planar and tomographic) was assessed after intravenous injection of 10 mCi of 99mTc-anti-TNF-α. Orbits and cerebral hemispheres were defined as regions of interest (ROIs) to enable orbit/hemisphere ROI-ratios of total radioactive uptake. ROI-ratios were considered positive at >2·5. Average total radiation uptake (TRU) was also determined for each orbit (AVGROI ). Clinical, laboratory and SCI data were compared between responders (CAS became inactive) and non-responders to CorT (18 patients). At baseline, AVGROI were higher in active OG orbits (67·3 cps) than in inactive ones (33·6 cps; P<0·05). AVGROI (absolute values) reduced (-29·9 cps) in CorT responders and tended (P = 0·067) to differ from variations occurred in non-responders (+6·9 cps in patients with maintained CAS positivity post-treatment). Higher baseline ROI-ratios (4·9 versus 3·3; P = 0·056) and its pronounced reductions following CorT (-37% versus +56% in non-responders; P = 0·036) tended to be associated with good CorT responses in the subgroup of GO history ≥1 year. SCI showed a good association with active eye disease and may be an additional tool to identify CorT responders.
Assuntos
Adalimumab/administração & dosagem , Corticosteroides/uso terapêutico , Oftalmopatia de Graves/diagnóstico por imagem , Oftalmopatia de Graves/tratamento farmacológico , Compostos Radiofarmacêuticos/administração & dosagem , Tecnécio/administração & dosagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Feminino , Oftalmopatia de Graves/imunologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Indução de Remissão , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologiaRESUMO
A range of antitumor agents for cancer treatment is available; however, they show low specificity, which often limit their use. Recently, we have reported the preparation of folate-coated long-circulating and pH-sensitive liposomes (SpHL-folate-PTX) loaded with paclitaxel (PTX), an effective drug for the treatment of solid tumors, including breast cancer. The purpose of this study was to prepare and characterize SpHL-PTX and SpHL-folate-PTX radiolabeled with technetium-99m (99mTc). Biodistribution studies and scintigraphic images were performed after intravenous administration of 99mTc-PTX, 99mTc-SpHL-PTX and 99mTc-SpHL-folate-PTX into healthy and tumor-bearing mice. High radiochemical purity (>98%) and in vitro stability (>90%) were achieved for both liposome formulations. The pharmacokinetic properties of 99mTc-SpHL-DTPA-PTX and 99mTc-SpHL-folate-DTPA-PTX decreased in a monophasic manner showing half-life of 400.1 and 541.8min, respectively. Scintigraphic images and biodistribution studies showed a significant uptake in liver, spleen and kidneys, demonstrating these routes as way for excretion. At 8h post-injection, the liposomal tumor uptake was higher than 99mTc-PTX. Interesting, 4h after administration, the liposome folate coated showed higher tumor-to-muscle ratio than 99mTc-SpHL-DTPA-PTX and 99mTc-PTX. In conclusion, the liposomal systems, showed high tumor uptake by scintigraphic images, especially the 99mTc-SpHL-folate-DTPA-PTX that showed a sustained and higher tumor-to-muscle ratio than non-functionalized liposome, which indicate its feasibility as a PTX delivery system to folate positive tumors.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico/administração & dosagem , Paclitaxel/administração & dosagem , Tecnécio/administração & dosagem , Animais , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/metabolismo , Feminino , Ácido Fólico/sangue , Humanos , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Paclitaxel/sangue , Tecnécio/sangue , Distribuição TecidualRESUMO
Lymph node metastases are an independent prognosis factor in gastric carcinoma (GC) patients. Radical lymphadenectomy can improve survival but it can also increase surgical morbidity. As a principle, sentinel node (SN) navigation surgery can avoid unnecessary lymphadenectomy without compromising prognosis. In this pilot study, 24 patients with untreated GC were initially screened for SN navigation surgery, of which 12 were eligible. Five patients had T2 tumors, 5 had T3 tumors and 2 had T1 tumors. In 33% of cases, tumor diameter was greater than 5.0 cm. Three hundred and eighty-seven lymph nodes were excised with a median of 32.3 per patient. The SN navigation surgery was feasible in all patients, with a median of 4.5 SNs per patient. The detection success rate was 100%. All the SNs were located in N1 and N2 nodal level. In 70.9% of cases, the SNs were located at lymphatic chains 6 and 7. The SN sensitivity for nodal staging was 91.6%, with 8.3% of false negative. In 4 patients who were initially staged as N0, the SNs were submitted to multisection analyses and immunohistochemistry, confirming the N0 stage, without micrometastases. In one case initially staged as negative for nodal metastases based on SN analyses, metastases in lymph nodes other than SN were found, resulting in a 20% skip metastases incidence. This surgery is a reproducible procedure with 100% detection rate of SN. Tumor size, GC location and obesity were factors that imposed some limitations regarding SN identification. Results from nodal multisection histology and immunohistochemistry analysis did not change initial nodal staging.
Assuntos
Carcinoma/cirurgia , Corantes de Rosanilina/administração & dosagem , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Gástricas/cirurgia , Tecnécio/administração & dosagem , Carcinoma/patologia , Corantes/administração & dosagem , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Gradação de Tumores , Assistência Perioperatória/métodos , Projetos Piloto , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/patologiaRESUMO
Gliomas are the most common type among all central nervous system tumors. The aggressiveness of gliomas is correlated with the level of angiogenesis and is often associated with prognosis. The aim of this study is to evaluate the novel GX1 peptide and the heterodimer RGD-GX1 radiolabeled with technetium-99m, for angiogenesis detection in glioma models. Radiolabeling and radiochemical controls were assessed for both radioconjugates. In vitro binding studies in glioma tumor cells were performed, as well as biodistribution in SCID mice bearing tumor cells, in order to evaluate the biological behavior and tumor uptake of the radiocomplexes. Blocking and imaging studies were also conducted. MicroSPECT/CT images were acquired in animals with experimentally implanted intracranial tumor. Open field activity was performed to evaluate behavior, as well as perfusion and histology analysis. The radiochemical purity of both radiotracers was greater than 96 %. In vitro binding studies revealed rather similar binding profi le for each molecule. The highest binding was for RGD-GX1 peptide at 120 min in U87MG cells (1.14 ± 0.35 %). Tumor uptake was also favorable for RGD-GX1 peptide in U87MG cells, reaching 2.96 ± 0.70 % at 1 h p.i. with 47 % of blocking. Imaging studies also indicated better visualization for RGD-GX1 peptide in U87MG cells. Behavior evaluation pointed brain damage and histology studies confirmed actual tumor in the uptake site. The results with the angiogenesis seeking molecule (99m)Tc-HYNIC-E-[c(RGDfk)-c(GX1)] were successful, and better than with (99m)Tc-HYNIC-PEG4-c(GX1). Future studies targeting angiogenesis in other glioma and nonglioma tumor models are recommended.
Assuntos
Glioma/diagnóstico por imagem , Neovascularização Patológica/diagnóstico por imagem , Oligopeptídeos/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Glioma/diagnóstico , Glioma/metabolismo , Humanos , Camundongos , Camundongos SCID , Neovascularização Patológica/metabolismo , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Tecnécio/administração & dosagem , Tecnécio/química , Tecnécio/metabolismo , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Lymph node metastases are an independent prognosis factor in gastric carcinoma (GC) patients. Radical lymphadenectomy can improve survival but it can also increase surgical morbidity. As a principle, sentinel node (SN) navigation surgery can avoid unnecessary lymphadenectomy without compromising prognosis. In this pilot study, 24 patients with untreated GC were initially screened for SN navigation surgery, of which 12 were eligible. Five patients had T2 tumors, 5 had T3 tumors and 2 had T1 tumors. In 33% of cases, tumor diameter was greater than 5.0 cm. Three hundred and eighty-seven lymph nodes were excised with a median of 32.3 per patient. The SN navigation surgery was feasible in all patients, with a median of 4.5 SNs per patient. The detection success rate was 100%. All the SNs were located in N1 and N2 nodal level. In 70.9% of cases, the SNs were located at lymphatic chains 6 and 7. The SN sensitivity for nodal staging was 91.6%, with 8.3% of false negative. In 4 patients who were initially staged as N0, the SNs were submitted to multisection analyses and immunohistochemistry, confirming the N0 stage, without micrometastases. In one case initially staged as negative for nodal metastases based on SN analyses, metastases in lymph nodes other than SN were found, resulting in a 20% skip metastases incidence. This surgery is a reproducible procedure with 100% detection rate of SN. Tumor size, GC location and obesity were factors that imposed some limitations regarding SN identification. Results from nodal multisection histology and immunohistochemistry analysis did not change initial nodal staging.
Assuntos
Humanos , Corantes de Rosanilina/administração & dosagem , Neoplasias Gástricas/cirurgia , Carcinoma/cirurgia , Tecnécio/administração & dosagem , Biópsia de Linfonodo Sentinela/métodos , Carcinoma/patologia , Projetos Piloto , Corantes/administração & dosagem , Gradação de Tumores , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Metástase LinfáticaRESUMO
The use of in vivo assay to determine the biodistribution and subsequent inter-comparison with human parameters has been used since the dawn of science. The use of this type of test admits the metabolic equity among animals for inter-comparison. Thus, the use of Wistar rats in particular is quite frequent. Regarding routes of administration, there are three ways to test priority: jugular vein, intraocular (eye plexus) and caudal; there is a consensus that these three pathways behave in the same way, or at least very similar. Biodistribution studies of drugs, especially radiopharmaceuticals, have been using randomly any of these pathways believed to be effective in their likeness without worrying about your real analytic equity. In this study, we performed in vivo assay in 8 Wistar rats using 99mTc -labeled Herceptin to review the route of administration on the biodistribution result. Thus, four mice were injected via the intraocular (eye plexus), and four were injected via tail (caudal plexus). The results were quite disparate and call the attention of the scientific community to reassess the protocols for animal experiments, in order to have uniformity and fairness between the data and may represent a test for human inter-comparison of more reliable and trustworthy way.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacocinética , Bioensaio/métodos , Tecnécio/administração & dosagem , Tecnécio/farmacocinética , Animais , Feminino , Masculino , Taxa de Depuração Metabólica , Especificidade de Órgãos , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Wistar , Distribuição Tecidual , TrastuzumabRESUMO
In the present study, boron nitride nanotubes (BNNTs) were synthesized from an innovative process and functionalized with a glycol chitosan polymer in CDTN (Centro de Desenvolvimento da Tecnologia Nuclear) laboratories. As a means of studying their in vivo biodistribution behavior, these nanotubes were radiolabeled with (99m)Tc and injected in mice. Their size, distribution, and homogeneity were determined by photon correlation spectroscopy (PCS), while their zeta potential was determined by laser Doppler anemometry. The morphology and structural organization were evaluated by scanning electron microscopy (SEM). The functionalization in the nanotubes was evaluated by thermogravimetry analysis (TGA) and Fourier transformer infrared spectroscopy. The results showed that BNNTs were obtained and functionalized successfully, reaching a mean size and dispersity deemed adequate for in vivo studies. The BNNTs were also evaluated by ex vivo biodistribution studies and scintigraphic imaging in healthy mice. The results showed that nanostructures, after 24h, having accumulated in the liver, spleen and gut, and eliminated via renal excretion. The findings from this study reveal a potential application of functionalized BNNTs as new potential drugs or radioisotope nanocarriers to be applied in therapeutic procedures.
Assuntos
Compostos de Boro/farmacocinética , Portadores de Fármacos , Nanotubos , Tecnécio/farmacocinética , Animais , Compostos de Boro/administração & dosagem , Compostos de Boro/química , Química Farmacêutica , Quitosana/química , Composição de Medicamentos , Trato Gastrointestinal/diagnóstico por imagem , Trato Gastrointestinal/metabolismo , Injeções Intravenosas , Rim/diagnóstico por imagem , Rim/metabolismo , Fígado/diagnóstico por imagem , Fígado/metabolismo , Camundongos , Microscopia Eletrônica de Varredura , Nanotecnologia , Tamanho da Partícula , Cintilografia , Espectroscopia de Infravermelho com Transformada de Fourier , Baço/diagnóstico por imagem , Baço/metabolismo , Tecnécio/administração & dosagem , Tecnécio/química , Tecnologia Farmacêutica/métodos , Termogravimetria , Distribuição TecidualRESUMO
OBJETIVO: Determinar, experimentalmente, os coeficientes de recuperação do 111In e do 99mTc usando imagens SPECT. MATERIAIS E MÉTODOS: Quatro diferentes concentrações de 111In e de 99mTc foram usadas para quantificar a atividade em esferas de diferentes tamanhos. As imagens foram obtidas com um equipamento híbrido SPECT/CT, com dois detectores. A reconstrução das imagens foi realizada usando o método iterativo ordered subset expectation maximization (OSEM). A correção de atenuação foi realizada com o uso de um mapa de atenuação e a correção de espalhamento foi realizada usando a técnica das janelas de energia. RESULTADOS: Os resultados mostraram que o efeito do volume parcial foi observado de forma mais significativa para as esferas com volume < 6 ml. Para o 111In, os resultados mostram uma dependência com relação às concentrações usadas nas esferas e ao nível de background usado. Para o 99mTc, pôde-se observar uma tendência à subestimação dos resultados quando os níveis mais altos de background foram utilizados. CONCLUSÃO: É necessário usar os fatores de correção para compensar o efeito do volume parcial em objetos com volume < 6 ml para ambos os radionuclídeos. A subtração das contagens espúrias presentes nas imagens SPECT foi o fator que mais influenciou na quantificação da atividade nessas esferas.
OBJECTIVE: To experimentally determine the 99mTc and 111In activity recovery coefficients in SPECT imaging. MATERIALS AND METHODS: Four different 99mTc and 111In concentrations were utilized for quantifying activity in spheres of four different sizes. Images were obtained with a hybrid dual-head SPECT-CT imaging system. The ordered subset expectation maximization (OSEM) iterative method was utilized for images reconstruction. An attenuation map was utilized for attenuation correction, and the multiple energy window technique for scattering correction. RESULTS: Results for spheres < 6 ml in volume were significantly affected by the partial volume effect. For 111In quantification, results show a dependence on sphere concentrations and background levels. For 99mTc quantification, there was a tendency towards values underestimation with higher background levels. CONCLUSION: Correction factors must be utilized for compensating the partial volume effect on objects with < 6 ml in volume for both radionuclides. Background subtraction to compensate spurious count present on SPECT images has a significant influence on the quantification of activity, especially for the smaller objects.
Assuntos
Índio/administração & dosagem , Tecnécio/administração & dosagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Medicina Nuclear/métodos , Radioisótopos/administração & dosagem , Radioisótopos/efeitos da radiaçãoRESUMO
El propósito de este estudio fue comparar la sobrevida en pacientes con ganglios negativos en quienes se realizó la biopsia del ganglio centinela, con un grupo de control histórico que tenían ganglios axilares negativos, a quienes se les practicó vaciamiento axilar de los niveles I-II, en la era antes de la utilización del ganglio centinela. En nuestra unidad revisamos la historia y datos de 295 pacientes en quienes se practicó mastectomía parcial oncológica con vaciamiento axilar de rutina de los cuales 187 pacientes eran linfonódulos negativos y los comparamos con 180 pacientes a quienes se les practicó mastectomía parcial oncológica y biopsia de ganglio centinela, con la combinación azul + tecnecio 99, de los cuales 156 eran ganglios negativos. La sobrevida para las pacientes a las cuales se les realizó vaciamiento axilar fue de (67 por ciento) y en el grupo de pacientes a quienes se le practicó el ganglio centinela fue de (70,1 por ciento) comparándolas no encontramos diferencias estadísticamente significativas. El ganglio centinela ha demostrado ser un método exacto para estatificar la axila y puede reemplazar la práctica rutinaria del vaciamiento axilar.
The purpose of this study was to compare the survival of patients with nodes negatives that underwent sentinel node detection, and the result was compare with a historic control group with negative axillaries nodes, which we realized a axillaries dissection to the levels I and II, according to the costume of pre sentinel node era. In our unit, we revised the files of 295 patients in whom partial oncology mastectomy with routine axillaries dissection was routine performed, in 187 of them were found lymph nodes negative, and we compared them with a 180 patients who underwent partial oncology mastectomy and sentinel node biopsy, with a combination of blue dye + technetium 99 of which 156 patients were lymph nodes negative. The survival in patients with axillaries dissection was (67 %) and in the group of patients that we practice sentinel node the survival were (70.1 %). When we compare both, there was not statistically significant. The sentinel node method has demonstrated to be an exact procedure for the staging of the axils and can replace the routine practice of the axillaries dissection.
Assuntos
Humanos , Feminino , Biópsia de Linfonodo Sentinela/métodos , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Tecnécio/administração & dosagem , Mastectomia Segmentar , Excisão de Linfonodo , Estimativa de Kaplan-Meier , OncologiaRESUMO
No sentido de comparar os métodos de corante vital e radioguiado para identificar linfonodo sentinela e determinar a eficácia do exame histológico intra-operatório ou de congelação do linfonodo sentinela em relação ao exame histológico definitivo, foi realizado estudo descritivo, prospectivo, tipo série de casos. Oitenta e seis pacientes com câncer da mama, atendidos no Serviço de Mastologia da Clínica Professor Antônio Simão dos Santos Figueira Filho, entre janeiro de 1999 e outubro de 2002, foram divididos em: Grupo 1 Submetidos à técnica do azul patente; e Grupo II ao método radioguiado. Os dois grupos não diferiram quanto à detecção do câncer da mama, à imagem mamográfica, ao estadiamento lesional e clínico e às características dos linfonodos sentinelas. Embora o método radioguiado tenha apresentado acurácia e exatidão maiores que do azul patente, não houve diferença estatisticamente significante. Comprovou-se que ambos os métodos são inócuos, de fácil execução, reprodutíveis e confiáveis na definição da abordagem do linfonodo sentinela da mama. Recomenda-se a identificação do linfonodo sentinela pelo método do azul patente nas regiões em que não se tenha medicina nuclear, realizada por mastologia comprovadamente capacitado em centro de referência, após ter cumprido a curva de aprendizado.
To compare vital dye method and radioguided for the identification of sentinel limph node, as well as to determine the efficacy of intra surgery histological examination of sentinel lymph node, compared to histological definitive examination, the authors performed a descriptive, prospective, serie of cases. Eighty six patients, at Mastology Service at Professor Antonio Simão dos Santos Figueira Filho Clinic, from January 1999 to October 2002, with mammary tumors, were divided into two groups: group I of patients submitted to blue dye technique for detecting sentinel lymph node and and group II, submitted to radioguided technique. The groups did not differ on technique for breast cancer diagnosis, mammography images characteristics, clinical and lesional stage and sentinel lymph nodes characteristics. Although radioguided technique presented accuracy as well as exactitude higher than patent blue technique, these differences had no statistical significance. The authors concluded that both methods are innocuous, easy to perform, reproducible and secure for the detection of mammary sentinel lymph node and suggested the utilization of patent blue technique for detecting sentinel lymph nodes in regions where nuclear medicine are not available, performed by a mastologist, trained and capable, after completing the learning curve.
Assuntos
Humanos , Feminino , Corantes/administração & dosagem , Corantes , Biópsia de Linfonodo Sentinela/métodos , Linfonodos , Linfonodos/patologia , Neoplasias da Mama/patologia , Radiocirurgia , Diagnóstico por Imagem , Metástase Linfática/diagnóstico , Neoplasias da Mama/cirurgia , Tecnécio/administração & dosagemRESUMO
Este estudo teve como objetivo avaliar a força muscular respiratória (FMR) por meio de manovacuometria de homens e mulheres com idade entre 40 e 89 anos, verificando se há diferenças nos valores da pressão inspiratória máxima...
The purpose of the study was to assesss respiratory muscle strength (RMS) by means of manovacuometry among women and men aged 40-89, checking whether there are differences in maximal inspiratory pressure...
Assuntos
Humanos , Feminino , Aerossóis/administração & dosagem , Nebulizadores e Vaporizadores , Respiração com Pressão Positiva , Aerossóis/efeitos adversos , Pulmão , Tecnécio/administração & dosagemRESUMO
PURPOSE: To study which of the two most used radiopharmaceutical drugs for the sentinel lymph node (SLN) biopsy procedure (dextran 500 99mTc and phytate 99mTc) best defines the SLN and migrates less to other lymph nodes. MATERIAL AND METHODS: Thirty-two rats, separated into two groups, underwent lymphoscintigraphy examination with either dextran or phytate followed by sentinel (popliteal), lumbar, and inguinal lymph node biopsy. Radiation was detected with a gamma probe. RESULTS: The statistical study indicated count rates significantly higher in the SLN than in the other basins for both the dextran (P<0.01) and phytate groups (P<0.001). There was no statistically significant difference concerning SLN absorption in either group (P=0.2981). In the dextran group, migration occurred to 1.5 lymphatic basins with counting higher than 10% of that found in the SLN versus 0.8 in the phytate group (P=0.0023). Migration was thus higher in the dextran group (P=0.0207). CONCLUSION: There was no statistically significant difference between dextran and phytate in the SLN identification, but the phytate migrated to fewer lymphatic basins beyond the SLN and with less intensity.
Assuntos
Dextranos/administração & dosagem , Linfonodos/diagnóstico por imagem , Ácido Fítico/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Biópsia de Linfonodo Sentinela/métodos , Tecnécio/administração & dosagem , Animais , Dextranos/farmacocinética , Masculino , Ácido Fítico/farmacocinética , Cintilografia , Ratos , Ratos Wistar , Tecnécio/farmacocinética , Distribuição Tecidual/fisiologiaRESUMO
The relevance of certain gangliosides in tumour growth and metastatic dissemination has been well documented, reasons for considering these molecules as potential targets for cancer immunotherapy and diagnosis. GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues according to immunohistochemical studies, using either polyclonal or monoclonal antibodies. But both immunohistochemical and biochemical methods have strongly suggested its over-expression in human breast tumours. Nevertheless, the lack of a direct evidence of this antigenic display in human breast cancer has kept the subject controversial. For the first time, we described herein the "in vivo" detection of GM3(NeuGc) ganglioside in human breast primary tumours using a radioimmunoscintigraphic technique with 14F7, a highly specific anti-GM3(NeuGc) ganglioside monoclonal antibody, labelled with (99m)Tc. In an open, prospective Phase I/II clinical trial, including women diagnosed in stage II breast cancer, the 14F7 monoclonal antibody accumulation in tumours at doses of 0.3 (n=5), 1 (n=5) and 3 mg (n=4) was evaluated. Noteworthy, the immunoscintigraphic study showed antibody accumulation in 100% of patients' tumours for the 1 mg dose group. In turn, the radioimmunoconjugate injected at doses of 0.3 mg or 3 mg of the antibody, was uptaken by 60 and 33.3% of breast tumours, respectively. "In vivo" immune recognition of GM3(NeuGc) in breast tumours reinforces the value of this peculiar target for cancer immunotherapy.
Assuntos
Anticorpos Monoclonais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Gangliosídeo G(M3)/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Radioimunodetecção , Tecnécio/administração & dosagemRESUMO
Objetivo: verificar o sucesso da localização do linfonodo sentinela (LS) com injeção periareolar de azul patente V em casos de carcinoma de mama, correlacionando-o a variáveis como, idade, tamanho da lesão, resultado da linfocintilografia pré-operatória, localização e grau histopatológico do tumor. A injeção peritumoral de 99mTc-fitato, realizada simultaneamente em toda a amostra - considerada padrão-ouro - permitiu o cálculo da sensibilidade da via periareolar e avaliar se os mesmos LSs eram marcados por ambas as técnicas. Métodos: realizaram-se 54 procedimentos para a biópsia do linfonodo sentinela (BLS) após injeções de 0,1 mCi de 99mTc-fitato, via peritumoral, seguidas de linfocintilografias mamárias, e de 2 mL de azul patente V periareolar. Resultados: as injeções com o corante conseguiram êxito em 53 casos (98,15 por cento) versus 50 (92,59 por cento) no método radioguiado, e no único insucesso do azul patente V também não houve marcação com o 99mTc-fitato. A sensibilidade da injeção periareolar foi de 100 por cento. Entre as variáveis, somente o resultado da linfocintilografia influiu significativamente na marcação do LS por ambos os métodos. Conclusão: a injeção periareolar conseguiu marcar o mesmo LS que a peritumoral, a despeito da localização do tumor. Tal constatação é importante, pois a via periareolar é mais simples, de rápido aprendizado e em lesões impalpáveis dispensa métodos especiais.
Assuntos
Biópsia de Linfonodo Sentinela/métodos , Injeções Intradérmicas , Linfonodos/patologia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Tecnécio/administração & dosagem , Tecnécio , Corantes/administração & dosagem , CorantesRESUMO
OBJECTIVE: To evaluate the efficacy of three frequently used spacer devices to deliver aerosol to the lung, and to compare radioaerosol deposition with each device in different age groups. METHODS: Nine healthy, non-smoking volunteers were recruited: three adults and six children, including three toddlers and three school age children. Qualitative and semi-quantitative analysis of radioaerosol deposition in the lung were carried out. Yet, two small-volume devices (Aerochamber and Inal-Air) and one large-volume device (Flumax) were compared. Each patient inhaled 99mtechnetium-phytate. The device was filled during 30 seconds with radioaerosol. Oxygen was used as the driving gas. During 10 seconds, the patients inhaled the radioaerosol. The radiation emitted at the front and back of the chest was measured. The radiation inside the device was also measured. RESULTS: The quantitative evaluation of lung deposition revealed that the younger the patient, the less aerosol was deposited in the lung with the large-volume spacer device (Flumax). The difference between small-volume devices (Aerochamber and Inal-Air) was not significant. CONCLUSION: Small-volume spacers are the most appropriate for children. Large-volume devices should only be used by adolescents and adults.
Assuntos
Espaçadores de Inalação , Pulmão , Tecnécio/administração & dosagem , Administração por Inalação , Adulto , Aerossóis , Fatores Etários , Criança , Pré-Escolar , Humanos , Pulmão/química , Tecnécio/análiseRESUMO
OBJETIVO: Avaliar, através de estudo da deposição pulmonar de 99m tecnécio-fitato, a eficácia de três espaçadores freqüentemente utilizados na prática clínica e comparar esta deposição de acordo com diferentes faixas etárias. MÉTODOS: Nove pacientes voluntários sadios, sem história de doença pulmonar, foram estudados, sendo três adultos e seis crianças de diferentes faixas etárias. Através de verificação qualitativa e semiquantitativa da deposição de 99m tecnécio-fitato em vias aéreas, procedeu-se a análise comparativa entre dois espaçadores de pequeno volume (Aerochamber® e Inal-Air®) e um espaçador de grande volume (Flumax®). Cada paciente recebeu inalação de 99m tecnécio-fitato. O espaçador foi preenchido, durante 30 segundos, por radioaerossóis impulsionados por fluxo de oxigênio. Por 10 segundos, os pacientes procederam à inalação com máscara acoplada ao espaçador. Por 4 minutos, realizou-se contagem de radiação emitida nas faces anterior e posterior do tórax. Realizou-se, ainda, contagem de radiação presente no interior de cada espaçador. RESULTADOS: Na avaliação semiquantitativa da deposição pulmonar, verificou-se que, em todas as faixas etárias, houve uma menor deposição percentual quando se utilizou o espaçador de grande volume (Flumax®), sendo esta diferença relativa inversamente proporcional à faixa etária. Em outras palavras, quanto menor a criança, menor a deposição de aerossol radioativo ao se utilizar espaçadores de grande volume. Por outro lado, não se verificou diferença significativa entre os espaçadores de pequeno volume (Inal-Air® e Aerochamber®) nas faixas etárias estudadas. CONCLUSAO: Os dados obtidos indicam que espaçadores de pequeno volume são os mais indicados para utilização na faixa pediátrica, devendo-se restringir o uso de espaçadores de grande volume a adolescentes e adultos.
Assuntos
Humanos , Pré-Escolar , Criança , Adulto , Espaçadores de Inalação , Pulmão/química , Tecnécio/análise , Administração por Inalação , Aerossóis , Fatores Etários , Pulmão/efeitos da radiação , Terapia Respiratória , Tecnécio/administração & dosagemRESUMO
Monoclonal Antibody (mAb) ior C5 is a murine IgG(1) that recognizes the tumor associated antigen (TAA) ior C2, a cell surface O-linked glycoprotein carbohydrate chain not present in most normal tissues and homogeneously expressed in the cytoplasm of normal colon epithelium and heterogeneously expressed in more than 83% of primary colorectal carcinomas. This study was designed to investigate the pharmacokinetics, biodistribution and the absorbed radiation doses of (99m)Tc-labeled mAb ior C5 antibody in colorectal tumor patients. Ten patients were administered 3 mg of anti-O-linked glycoprotein carbohydrate chain TAA ior C2 murine monoclonal antibody ior C5 radiolabeled with (99m)Tc activity of 1435.0 +/- 123 MBq by intravenous (i.v.) bolus infusion. Blood and urine samples were collected from 4 out of 10 patients at timed intervals from 10 min and up to 24 h after injection of the (99m)Tc-labeled mAb ior C5 for pharmacokinetic studies. Whole body images were taken in 5 out of 10 patients for quantitative normal organ biodistribution and dosimetry studies and planar anterior and posterior and SPECT images were taken in 5 out of 10 patients for tumor localization. Mean absorbed doses were estimated using the methods developed by the Medical Internal Radiation Dose (MIRD) committee. The effective dose equivalent (EDE) and effective dose (ED) were calculated as prescribed in International Commission on Radiological Protection (ICRP) publications 30 and 60. Plasma disappearance curves of (99m)Tc-labeled murine antibody ior C5 were best fit by a two-compartment model in all patients with (t(1/2alpha)) of 4.32 +/- 2.18 h and (t(1/2beta) of 32.6 +/- 3.82 h. Among the main target organs, accumulation of the radiolabeled antibody was found in liver (9.38 +/- 0.80%), heart (8.92 +/- 0.94%) and spleen (1.37 +/- 0.30%) at 5 min post-administration. These values were reduced at 24 h to (5.91 +/- 0.73%) and (0.62 +/- 0.22%), respectively, for the heart and spleen and increased to (9.78 +/- 1.99%) for liver. Estimates of radiation absorbed dose to normal organs in rad/mCi administered were: whole body, 0.0181 +/- 0.0017; heart wall, 0.0768 +/- 0.0090; kidneys, 0.0530 +/- 0.0260; liver, 0.0565 +/- 0.0109 and spleen, 0.0540 +/- 0.0128. The effective dose equivalent and effective dose estimates for adults were 0.0314 +/- 0.0031 and 0.0249 +/- 0.0027 rem/mCi administered. This feasibility study indicates that the O-linked glycoprotein carbohydrate chain TAA ior C2 is expressed in primary and metastatic colorectal carcinomas and shows very limited expression in normal adult tissues. The very good pattern of biodistribution of (99m)Tc-labeled mAb ior C5 in patients will allow imaging of colorectal carcinoma lesions.
Assuntos
Anticorpos Monoclonais/farmacocinética , Neoplasias Colorretais/diagnóstico , Complemento C5/farmacocinética , Dosagem Radioterapêutica , Tecnécio/farmacocinética , Distribuição Tecidual , Idoso , Animais , Anticorpos Monoclonais/administração & dosagem , Antígenos Glicosídicos Associados a Tumores/química , Antígenos Glicosídicos Associados a Tumores/genética , Complemento C5/administração & dosagem , Cuba , Estudos de Viabilidade , Feminino , Meia-Vida , Corpo Humano , Humanos , Injeções Intravenosas , Masculino , Camundongos , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/urina , Tecnécio/administração & dosagemRESUMO
Animal models are currently used to verify the biodistribution of different radiopharmaceuticals before its clinical application in Nuclear Medicine; however, there may be some limitations. The utilization of labelled anti-tumor monoclonal antibodies (MoAb) in experimental models often requires implant of human antigens (usually a cellular implant), which cannot be achieved in immunocompetent animals. Our purpose was to label an anti-CEA MoAb with technetium-99m (99Tc) and to validate a simplified animal model using a noncellular antigenic implant. MoAb was directly labelled with 99mTc, after reduction with 2-mercaptoethanol. Labeling efficiency was checked by ascending chromatography and immunoreactive fraction was measured in plastic wells sensitized with the antigen. Radiopharmaceutical biodistribution was evaluated by dissection and scintigraphy in 5 mice groups; following the subcutaneous administration of Al(OH)3, CEA adsorbed Al(OH)2 and a control group evaluation. Labeling efficiency was 94+/-3%, which showed to be stable for 24 hr, with immunoreactive fraction above 50%. Invasive biodistribution evaluation showed prolonged blood retention, hepatic and renal uptake. A significant increase in uptake was observed in scintigraphic studies of animals with CEA-adsorbed Al(OH)3 implants compared with the other groups (p<0.05). The non-cellular antigenic implant model simplifies the pre-clinical evaluation of labelled MoAb.