RESUMO
Malaria-associated acute respiratory distress syndrome (ARDS) is an inflammatory disease causing alveolar-pulmonary barrier lesion and increased vascular permeability characterized by severe hypoxemia. Computed tomography (CT), among other imaging techniques, allows the morphological and quantitative identification of lung lesions during ARDS. This study aims to identify the onset of malaria-associated ARDS development in an experimental model by imaging diagnosis. Our results demonstrated that ARDS-developing mice presented decreased gaseous exchange and pulmonary insufficiency, as shown by the SPECT/CT technique. The pulmonary aeration disturbance in ARDS-developing mice on the 5th day post infection was characterized by aerated tissues decrease and nonaerated tissue accumulation, demonstrating increased vascular permeability and pleural effusion. The SPECT/CT technique allowed the early diagnosis in the experimental model, as well as the identification of the pulmonary aeration. Notwithstanding, despite the fact that this study contributes to better understand lung lesions during malaria-associated ARDS, further imaging studies are needed.
Assuntos
Pulmão/diagnóstico por imagem , Malária/complicações , Síndrome do Desconforto Respiratório/complicações , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Parasitemia/complicações , Perfusão , Análise de Sobrevida , Tecnécio/metabolismoRESUMO
Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Anticorpos Monoclonais Humanizados/análise , Receptores ErbB/análise , Hidrazinas/análise , Imagem Molecular/métodos , Ácidos Nicotínicos/análise , Tecnécio/análise , Animais , Anticorpos Monoclonais Humanizados/metabolismo , Anticorpos Monoclonais Humanizados/farmacocinética , Receptores ErbB/metabolismo , Humanos , Hidrazinas/metabolismo , Hidrazinas/farmacocinética , Camundongos , Ácidos Nicotínicos/metabolismo , Ácidos Nicotínicos/farmacocinética , Papaína/metabolismo , Cintilografia/métodos , Tecnécio/metabolismo , Tecnécio/farmacocinética , Distribuição TecidualRESUMO
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
The relationship between gastric emptying dysfunction and blood glucose concentration in elderly with type 2 diabetes mellitus was investigated, and the effect of rehabilitation exercise prescription training on gastric emptying in the geriatric diabetic patients was evaluated. A total of 160 older type 2 diabetic adults and 30 cases of non-diabetic patients were studied with regard to the gastric half emptying time (GET1/2) of solid meals radiolabelled with 99mTc. Eighty delayed gastric emptying diabetic patients were randomly divided into 4 four groups: rehabilitation exercise + mosapride group (N = 20), rehabilitation exercise group (N = 20), mosapride group (N = 20), and control group (N = 20). The level of blood glucose was measured every six months in a two-year follow-up. The solid GET1/2 of regulated blood glycemic control patients showed no statistically significant differences from non-diabetic patients (P > 0.05). However, the value for poor blood glycemic control patients exhibited significant statistical differences compared with both non-diabetic (P < 0.01) and regulated blood glycemic control group patients (P < 0.01). It showed that the gastric emptying time improved in the rehabilitation exercise group, mosapride group and rehabilitation exercise group + mosapride group after two years of treatment (P < 0.05). Fasting blood glucose in both rehabilitation exercise group and rehabilitation exercise + mosapride group was significantly decreased. Postprandial blood glucose in the rehabilitation exercise group, mosapride group, rehabilitation exercise group + mosapride group was significantly decreased. High blood glucose level can delay gastric emptying in older type 2 diabetic patients. Gastric emptying and blood glucose control affect each other. It was shown that appropriate rehabilitation exercise combined with prokinetic agent may improve gastric emptying in some geriatric type 2 diabetic patients and help control their blood glucose.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/reabilitação , Esvaziamento Gástrico , Adulto , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Feminino , Humanos , Masculino , Período Pós-Prandial , Cintilografia , Tecnécio/metabolismo , Fatores de TempoAssuntos
Adenocarcinoma/diagnóstico por imagem , Anticorpos Monoclonais Humanizados , Neoplasias Ósseas/diagnóstico , Neoplasias do Colo/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Tecnécio , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Anticorpos Monoclonais Humanizados/química , Anticorpos Monoclonais Humanizados/metabolismo , Bevacizumab , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/secundário , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Tecnécio/química , Tecnécio/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Vascular endothelial growth factor (VEGF) is one of the classic factors involved in tumor-induced angiognesis in several solid tumors. Bevacizumab, a monoclonal antibody against VEGF, can be used as an imaging tool in preclinical studies. The aim of this study was to radiolabel Bevacizumab with (99m)Tc and to evaluate in vivo its imaging properties in an adenocarcinoma animal model. For this purpose, Bevacizumab was derivatized with Suc-HYNIC as a bifunctional coupling agent. A mixture of Tricine/SnCl(2).2H(2)O was added to Bevacizumab-HYNIC and radiolabeled with (99m)TcO(4)(-). The radiochemical stability of the radiolabeled antibody was assessed. Biodistribution and scintigraphy imaging were performed in normal CD1 female mice and in spontaneous adenocarcinoma tumor bearing CD1 mice (n = 5). We demonstrated that 99mTc-HYNIC-Bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of (99m)Tc-HYNIC-Bevacizumab was 1.37 ± 0.51% and 5.33 ± 2.13% at 4 and 24 h postinjection, respectively. Scintigraphy image studies showed tumor selective uptake of (99m)Tc-HYNIC-Bevacizumab in the tumor-bearing mice. We conclude that (99m)Tc-HYNIC-Bevacizumb has the potential to be used as a tracer for tumor imaging in preclinical studies.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Inibidores da Angiogênese/farmacocinética , Anticorpos Monoclonais Humanizados/farmacocinética , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Tecnécio/farmacocinética , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/metabolismo , Animais , Anticorpos Monoclonais Humanizados/metabolismo , Bevacizumab , Estudos de Casos e Controles , Estudos de Viabilidade , Feminino , Camundongos , Cintilografia , Tecnécio/metabolismo , Distribuição TecidualRESUMO
Lectins, proteins that recognize carbohydrates, have been immobilized on inert supports and used in the screening or purification of glycoproteins. Anacardium occidentale bark infusion has been used as a hypoglycemic agent in Brazil. The toxicity of natural products may be evaluated determining their capability to alter the biodistribution of technetium-99M ((99m)Tc). This work reports the isolation and characterization of a lectin from A. occidentale bark (AnocBL), its evaluation as an affinity support for glycoprotein isolation and lectin effect on the uptake of (99m)Tc by rat adipocytes. AnocBL was isolated from 80 % ammonium sulphate supernatant by affinity chromatography on fetuin-agarose. SDS-PAGE showed a single protein band of 47 kDa. The monossacharide L-arabinose and the glycoproteins fetuin, asialofetuin, ovomucoid, casein, thyroglobulin, peroxidase, fetal bovine serum and IgG inhibited the activity. The lectin activity was stable until 70 °C and at a pH range of 3.0-7.5. AnocBL-Sepharose column bound fetuin indicating that the lectin matrix may be used to obtain glycoconjugates of biotechnological interest. In vitro assay revealed that glucose and insulin increase (99m)Tc uptake by rat adipocytes. AnocBL decreases (99m)Tc uptake, and this effect was not detected in the presence of glucose. Fetuin inhibited AnocBL effect in all insulin concentrations.
Assuntos
Adipócitos/metabolismo , Anacardium/química , Lectinas/isolamento & purificação , Lectinas/farmacologia , Casca de Planta/química , Tecnécio/metabolismo , Adipócitos/efeitos dos fármacos , Anacardium/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Células Cultivadas , Feminino , Glucose/metabolismo , Insulina/metabolismo , Lectinas/química , Lectinas/metabolismo , Masculino , Casca de Planta/metabolismo , Ratos , Ratos WistarRESUMO
BACKGROUND: Primary hyperparathyroidism occurs in only 10%-30% of patients with multiple endocrine neoplasia type 2A (MEN2A), rarely as the sole clinical manifestation, and is usually diagnosed after the third decade of life. SUMMARY: A 5-year-old girl was referred for prophylactic thyroidectomy as she carried the p.C634R RET mutation. She was clinically asymptomatic, with a normally palpable thyroid and with the cervical region free of lymphadenopathy or other nodules. Preoperative tests revealed hypercalcemia associated with elevation of parathyroid hormone (PTH) (calcium = 11.2 mg/dL, calcium ion = 1.48 mmol/L, phosphorus = 4.0 mg/dL, alkaline phosphatase = 625 U/L, parathyroid hormone (PTH) PTH = 998 pg/mL). A thyroid ultrasound was normal and parathyroid scintigraphy with (99m)Tc-Sestamibi revealed an area of radioconcentration in the upper half of the left thyroid lobe suggesting hyperfunctioning parathyroid tissue. She underwent total thyroidectomy and parathyroidectomy and developed hypocalcemia. The anatomopathological examination showed no histopathological changes in the thyroid tissue and an adenoma of the parathyroid gland, confirming the diagnosis of hyperparathyroidism. CONCLUSIONS: Primary hyperparathyroidism can be a precocious manifestation of MEN2A. This case report highlights that asymptomatic hypercalcemia should be scrutinized in children related to patients with MEN2A who carry a mutation in the RET proto-oncogene, especially mutations in the codon 634, before the currently recommended age of 8 years.
Assuntos
Hiperparatireoidismo/diagnóstico , Neoplasia Endócrina Múltipla Tipo 2a/diagnóstico , Fosfatase Alcalina/metabolismo , Cálcio/química , Pré-Escolar , Códon , Feminino , Humanos , Hipercalcemia/sangue , Hipercalcemia/genética , Hiperparatireoidismo/complicações , Neoplasia Endócrina Múltipla Tipo 2a/complicações , Mutação , Hormônio Paratireóideo/sangue , Fósforo/metabolismo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-ret/genética , Tecnécio/metabolismoRESUMO
El objetivo del presente trabajo fue desarrollar un péptido híbrido, que presente una secuencia capaz de quelatar al 99mTc y otra con afinidad por el receptor de la vitronectina, que permita la detección in vivo de tumores malignos. El marcaje del péptido PICIC3 con 99mTc se realizó de forma directa. Se estudió la estabilidad del complejo en exceso de L-cisteína y en plasma, la unión a proteínas plasmáticas, el coeficiente de partición en el sistema NaCl 0.9 por ciento:n-octanol, la carga del complejo mediante electroforesis y la afinidad por el receptor de la vitronectina se valoró a partir de un ensayo de saturación con membranas de células B16-F10. Se determinó la biodistribución en ratones C57BL/6 con injertos de melanoma B16-F10. Conclusiones: El péptido desarrollado mostró una afinidad satisfactoria por el receptor de la vitronectina y que permitió la detección in vivo de los melanomas múridos del tipo B16-F10 en los ratones injertados.
The aim of the present work was to develop a hybrid peptide, with a sequence for the chelation of 99mTc and other with affinity for the vitronectine receptor, to allow in vivo detection of malignant tumors. 99mTc-labeling of peptide PICIC3 was directly performed. The stability in presence of L-cysteine excess and plasma of the complex, its binding to plasma proteins, the partition coefficient in NaCl 0.9 percent:n-octanol, the charge of the chelate by electrophoresis and the peptide affinity for the vitronectine receptor by a saturation assay using membranes of B16-F10 cells, were studied. Biodistribution in C57BL/6 mice injerted with melanoma B16-F10 was assessed. Conclusions: Developed peptide showed a satisfactory affinity for the vitronectine receptor and allowed in vivo detection of murine melanomas in mice with allografts.
Assuntos
Animais , Camundongos , /metabolismo , Melanoma Experimental , Melanoma Experimental/metabolismo , Peptídeos Cíclicos/farmacocinética , Tecnécio/farmacocinética , Distribuição Tecidual , Estabilidade de Medicamentos , Fatores de Tempo , Marcação por Isótopo/métodos , Peptídeos Cíclicos/metabolismo , Tecnécio/metabolismoRESUMO
Radionuclides are used in nuclear medicine by variety of diagnostic procedures. The labeling of red blood cells (RBC) with (99m)Tc is a current method applied in clinical nuclear medicine. Drugs can alter this labeling and modify the disposition of the radiopharmaceuticals. The influence of Rochagan on the labeling of blood constituents with (99m)Tc was reported. Samples of blood were incubated with different concentrations of Rochagan (0%; 6.25%; 12.5%; 25%; 50%; 100%). Stannous chloride and (99m)Tc (3.7MBq/mL) were added. Plasma (P) and (RBC) were isolated and precipitated with thricloroacetic acid 5%. The insoluble (IF) and soluble fractions (SF) were separated. The %ATI in RBC, IF-P and IF-RBC were calculated. The %ATI on RBC decreased significantly (p<0.05) from control to all concentrations of Rochagan, respectively: 90.15 + or - 0.14(control) to 70.80 + or - 4.21; to 64.36 + or - 0.33; to 57.30 + or - 1.56; to 50.28 + or - 2.71; to 42.41 + or - 2.24; on IF-RBC, respectively: 84.70 + or - 0.87(control) to 67.16 + or - 4.38; to 63.63 + or - 2.92; to 59.02 + or - 3.17; to 43.75 + or - 1.00; to 24.15 + or - 0.94 and also on IF-P, respectively: 83.46 + or - 1.09(control) to 50.90 + or - 3.36; to 35.46 + or - 4.13; to 35.78 + or - 2.31; to 28.74 + or - 3.09; to 19.66 + or - 1.34. The analyses were performed by T-Student and Mann Whitney tests, p<0.05. This effect was probably due to products present in Rochagan that may complex with ions or have a direct/indirect effect on intracellular stannous ion concentration.