RESUMO
Molecular imaging (MI) is a non-invasive growing technology that allows the investigation of cellular and molecular processes in basic and clinical research and medicine. Luminescent proteins and radionuclides can be associated to target molecules providing high-definition and real-time image of whole body in few minutes or hours. Several MI studies have enabled the determination of molecular partners, in vivo tracking, and fate of compounds in different disorders. Considering that galectins are multifaceted proteins with great impact in many biological events, here we describe methods and strategies to generate labeled galectins for in vivo non-invasive imaging studies.
Assuntos
Galectinas , Imagem Molecular , Proteínas LuminescentesRESUMO
Polymeric nanoparticles encompass micelles and dendrimers. They are used for improving or controlling the action of the loaded therapy or imaging agent, including radionuclides. Some radionuclides possess properties appropriate for simultaneous imaging and therapy of a disease and are therefore called theranostic. The diversity in core materials and surface modification, as well as radiolabeling strategies, offers multiples possibilities for preparing polymeric nanoparticles using radionuclides. The present review describes different strategies in the preparation of such nanoparticles and their applications in nuclear nanomedicine.
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Dendrímeros/química , Sistemas de Liberação de Medicamentos , Micelas , Radioisótopos/uso terapêutico , Nanomedicina Teranóstica , Animais , Humanos , Nanopartículas/químicaRESUMO
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
Pulse-chase radiolabeling of cells with radioactive amino acids is a common method for studying the biosynthesis of proteins. The labeled proteins can then be immunoprecipitated and analyzed by electrophoresis and gel imaging techniques. This chapter presents a protocol for the biosynthetic labeling and immunoprecipitation of pancreatic islet proteins which are known to be affected in disorders such as diabetes, obesity, and metabolic syndrome.
Assuntos
Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Marcação por Isótopo , Animais , Biomarcadores , Eletroforese , Imunoprecipitação , Técnicas de Imunoadsorção , Insulina/metabolismo , Marcação por Isótopo/métodos , Ratos , Radioisótopos de Enxofre/metabolismoRESUMO
The use of nanoparticles for diagnostic approaches leads to higher accumulation in the targeting tissue promoting a better signal-to-noise ratio and consequently, early tumor detection through scintigraphic techniques. Such approaches have inherent advantages, including the possibility of association with a variety of gamma-emitting radionuclides available, among them, Tecnethium-99m (99mTc). 99mTc is readily conjugated with nanoparticles using chelating agents, such as diethylenetriaminepentaacetic acid (DTPA). Leveraging this approach, we synthesized polymeric micelles (PM) consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000) functionalized with DTPA for radiolabeling with 99mTc. Micelles made up of DSPE-mPEG2000 and DSPE-PEG2000-DTPA had a mean diameter of â¼10nm, as measured by DLS and SAXS techniques, and a zeta potential of -2.7±1.1mV. Radiolabeled micelles exhibited high radiochemical yields and stability. In vivo assays indicated long blood circulation time (456.3min). High uptake in liver, spleen and kidneys was observed in the biodistribution and imaging studies on healthy and tumor-bearing mice. In addition, a high tumor-to-muscle ratio was detected, which increased over time, showing accumulation of the PM in the tumor region. These findings indicate that this system is a promising platform for simultaneous delivery of therapeutic agents and diagnostic probes.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Nanopartículas/química , Neoplasias/tratamento farmacológico , Polímeros/química , Radioisótopos/química , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Camundongos , Camundongos Endogâmicos BALB C , Micelas , Polietilenoglicóis/química , Distribuição Tecidual/fisiologiaRESUMO
Pulse-chase radiolabeling of cells with radioactive amino acids is a common method for tracking the biosynthesis of proteins. Radiolabeled newly synthesized proteins can be analyzed by a number of techniques such as two dimensional gel electrophoresis (2DE). This chapter presents a protocol for the biosynthetic labeling of pancreatic islets with 35S-methionine in the presence of basal and stimulatory concentrations of glucose, followed by subcellular fractionation to produce a secretory granule fraction and analysis of the granule protein contents by 2DE. This provides a means of determining whether or not the biosynthetic rates of the entire granule constituents are coordinately regulated.
Assuntos
Eletroforese em Gel Bidimensional/métodos , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Marcação por Isótopo , Vesículas Secretórias/metabolismo , Animais , Fracionamento Celular , Secreção de Insulina , Marcação por Isótopo/métodos , Ratos , Frações Subcelulares , Radioisótopos de EnxofreRESUMO
Pulse radiolabeling of cells with radioactive amino acids is a common method for tracking the biosynthesis of proteins. Specific proteins can then be immunoprecipitated and analyzed by electrophoresis and imaging techniques. This chapter presents a protocol for the biosynthetic labeling of pancreatic islets with 35S-methionine, followed by multiplex sequential immunoprecipitation of insulin and three other secretory granule accessory proteins. This provided a means of distinguishing those pancreatic islet proteins with different biosynthetic rates in response to the media glucose concentrations.
Assuntos
Imunoprecipitação/métodos , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Marcação por Isótopo , Vesículas Secretórias/metabolismo , Animais , Eletroforese/métodos , Secreção de Insulina , RatosRESUMO
A aterosclerose é caracterizada como uma doença imune-inflamatória crônica das artérias devido ao grande acúmulo de lipídios na íntima. Um dos fatores envolvidos na progressão da aterosclerose é a presença de uma subfração de partículas de lipoproteína de baixa densidade (LDL) com um grau mínimo de modificação, denominada LDL eletronegativa [LDL(-)], que possui propriedades pró-inflamatórias, apresenta maior retenção na íntima das artérias e maior tempo de permanência na circulação sanguínea, gerando respostas imuno-inflamatórias. Epítopos de anticorpos monoclonais importantes no reconhecimento das partículas de LDL(-) foram mapeados por phage display, gerando peptídeos mimotopos (P1A3 e P2C7) com potencial para acompanhamento da progressão da aterosclerose, sendo excelentes candidatos como radiotraçadores marcados com emissores de pósitrons para obtenção de imagens moleculares por tomografia por emissão de pósitrons (PET) associada à tomografia computadorizada (PET/CT). O peptídeo P1A3 foi radiomarcado com 64Cu através da complexação com o quelante DOTA, obtendo-se imagens por PET/CT da captação do peptídeo na região do arco aórtico de camundongos knockout para a apolipoproteína E (Apoe-/-) comparados com animais controle sem lesões ateroscleróticas. Antes da obtenção das imagens PET/CT, os peptídeos radiomarcados foram validados através de estudos de estabilidade e biodistribuição, acumulando-se rapidamente nos rins. Também foi sintetizado um nanocluster de ouro, marcado com 64Cu e funcionalizado com P1A3 em sua superfície, observando-se o maior direcionamento dos nanoclusters de ouro ligados ao P1A3 para a região das lesões ateroscleróticas do arco aórtico de camundongos Apoe-/-, comparado ao nanocluster controle. Os peptídeos P1A3 e P2C7 radiomarcados com 68Ga, foram também avaliados por imagens PET/CT em camundongos knockout para o gene do receptor da LDL (LDLr-/-) tratados ou não com dieta hipercolesterolêmica. As imagens PET/CT mostraram que os peptídeos marcados com 68Ga tiveram um aumento de captação na região do arco aórtico de camundongos LDLr-/- hipercolesterolêmicos em relação ao controle. Além disso, P2C7 foi radiomarcado com 99mTc e sua biodistribuição demonstrou uma relação maior de % atividade injetada (AI)/órgão da aorta/coração nos camundongos hipercolesterolêmicos, em concordância com a imagem obtida por SPECT (tomografia computadorizada por emissão de fóton único) que revelou maior captação no arco aórtico
Atherosclerosis is characterized as a chronic immune-inflammatory disease of the large arteries due to the accumulation of lipids in the intima. One of the factors involved in the progression of atherosclerosis is the presence of a subfraction of low-density lipoprotein (LDL) particles with a minimum degree of modification, called electronegative LDL [LDL (-)], which has proinflammatory properties, retention in the intima of the arteries and longer residence time in the blood circulation, generating immune-inflammatory responses. Epitopes of monoclonal antibodies important for the recognition of LDL(-) particles were mapped by phage display, generating mimotope peptides (P1A3 and P2C7) with potential to monitor the progression of atherosclerosis. These peptides are excellent candidates as radiotracers labeled with positron emitters to obtain molecular images by positron emission tomography (PET) associated with computed tomography (PET/CT). The P1A3 peptide was radiolabeled with 64Cu by complexation with the DOTA chelator to obtain PET/CT images of the peptide uptake in the aortic arch of apoliprotein E knockout mice (Apoe-/-) compared to control animals without atherosclerotic lesions. Prior to PET/CT imaging, radiolabeled peptides were validated by stability and biodistribution studies that indicated rapid accumulation in the kidneys. It was also synthesized a gold nanocluster, labeled with 64Cu and functionalized with P1A3 on its surface, observing the greater targeting of gold nanoclusters bound to P1A3 in the region of the atherosclerotic lesions of the aortic arch of Apoe-/- mice, compared to control nanocluster. The P1A3 and P2C7 peptides radiolabeled with 68Ga were also evaluated by PET imaging in LDL receptor gene knockout mice (LDLr-/-) treated or not with a hypercholesterolemic diet. PET/CT images showed that the 68Ga-labeled peptides had increased uptake in aortic arch of LDLr-/- hypercholesterolemic mice in relation to the control. Furthermore, the biodistribution of 99mTc-radiolabeled P2C7 showed a higher %ID (injected dose)/organ ratio of aorta/heart in hypercholesterolemic mice that was in accordance to SPECT (single photon emission computed tomography) imaging showing its higher uptake in the aortic arch
Assuntos
Animais , Masculino , Camundongos , Aterosclerose/patologia , Tomografia por Emissão de Pósitrons/instrumentação , Imagem Molecular , Peptídeos/metabolismo , Radioisótopos/metabolismo , Tomografia Computadorizada por Raios X/instrumentaçãoRESUMO
The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to ß-neurotoxins (ß-NTx). The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main ß-NTx of M. fulvius venom. ß-NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA) and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was 60%-78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD50) and PLA2 activity of bioconjugated ß-NTx decreased 3 and 2.5 times, respectively, in comparison with native ß-NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of ß-NTx-DTPA-(67)Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with (67)Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of ß-NTx-DTPA-(67)Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of ß-NTx-DTPA-(67)Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming.
Assuntos
Venenos Elapídicos/química , Gadolínio DTPA/farmacocinética , Sistema Linfático/metabolismo , Neurotoxinas/farmacocinética , Animais , Elapidae , Gadolínio DTPA/química , Dose Letal Mediana , Masculino , Camundongos , Imagem Molecular , Neurotoxinas/química , Neurotoxinas/toxicidade , Ratos Wistar , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Distribuição TecidualRESUMO
BACKGROUND: Natural products might alter the labeling of blood constituents with technetium-99m ((99m)Tc) and these results may be correlated with modifications of the shape of the red blood cells (RBC). The biodistribution of radiopharmaceuticals can be also altered. OBJECTIVE: This investigation aimed to determine biological effects of an aqueous extract of chamomile (CE). MATERIALS AND METHODS: To study the effect of the CE on the labeling of blood constituents with (99m)Tc, in vitro and in vivo assays were performed. The effect of the CE on the morphology of RBC was observed under light microscope. The images were acquired, processed, and the perimeter/area ratio of the RBC determined. To analyze the effect of the CE on biodistribution of the sodium pertechnetate (Na(99m)TcO4) in Wistar rats, these animals were treated or not with a CE. Na(99m)TcO4 was injected, the rats were sacrificed, the organs were removed, weighted and percentage of radioactivity/gram calculated. RESULT: In the in vitro experiment, the radioactivity on blood cells compartment and on insoluble fractions of plasma was diminished. The shape and the perimeter/area ratio of the RBC were altered in in vitro assays. An increase of the percentage of radioactivity of Na(99m)TcO4 was observed in stomach after in vivo treatment. CONCLUSION: These results could be due to substances of the CE or by the products of the metabolism of this extract in the animal organism. These findings are examples of drug interaction with a radiopharmaceutical, which could lead to misdiagnosis in clinical practice with unexpected consequences.
RESUMO
OBJECTIVES: Scintigraphy is generally not the first choice treatment for prostate cancer, although successful studies using bombesin analog radiopeptides have been performed. Recently, a novel peptide obtained using a phage display library demonstrated an affinity for prostate tumor cells. The aim of this study was to compare the use of a bombesin analog to that of a phage display library peptide (DUP-1) radiolabeled with technetium-99m for the treatment of prostate carcinoma. The peptides were first conjugated to S-acetyl-MAG3 with a 6-carbon spacer, namely aminohexanoic acid. METHODS: The technetium-99m labeling required a sodium tartrate buffer. Radiochemical evaluation was performed using ITLC and was confirmed by high-performance liquid chromatography. The coefficient partition was determined, and in vitro studies were performed using human prostate tumor cells. Biodistribution was evaluated in healthy animals at various time points and also in mice bearing tumors. RESULTS: The radiochemical purity of both radiotracers was greater than 95 percent. The DUP-1 tracer was more hydrophilic (log P = -2.41) than the bombesin tracer (log P = -0.39). The biodistribution evaluation confirmed this hydrophilicity by revealing the greater kidney uptake of DUP-1. The bombesin concentration in the pancreas was greater than that of DUP-1 due to specific gastrin-releasing peptide receptors. Bombesin internalization occurred for 78.32 percent of the total binding in tumor cells. The DUP-1 tracer showed very low binding to tumor cells during the in vitro evaluation, although tumor uptake for both tracers was similar. The tumors were primarily blocked by DUP1 and the bombesin radiotracer primarily targeted the pancreas. CONCLUSION: Further studies with the radiolabeled DUP-1 peptide are recommended. With further structural changes, this molecule could become an efficient alternative tracer for prostate tumor diagnosis.
Assuntos
Animais , Humanos , Masculino , Camundongos , Aminocaproatos/química , Bombesina , Oligopeptídeos/química , Peptídeos , Neoplasias da Próstata , Compostos Radiofarmacêuticos , Tecnécio , Aminocaproatos/farmacocinética , Bombesina/análogos & derivados , Meios de Cultura , Modelos Animais de Doenças , Marcação por Isótopo/métodos , Camundongos Nus , Oligopeptídeos/farmacocinética , Pâncreas , Distribuição Aleatória , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Receptores da Bombesina/análise , Receptores da Bombesina/metabolismo , Biomarcadores Tumorais/metabolismoRESUMO
Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m (99mTc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na99mTcO4)in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na99mTcO4 and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na99mTcO4 in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na99mTcO4 are conducted in patients who are using senna extract.
Assuntos
Animais , Masculino , Ratos , Células Sanguíneas/efeitos dos fármacos , Compostos Radiofarmacêuticos/farmacocinética , Extrato de Senna/farmacologia , Senna/química , /farmacocinética , Células Sanguíneas/metabolismo , Modelos Animais , Ratos Wistar , Compostos Radiofarmacêuticos/sangue , /sangue , Fatores de TempoRESUMO
OBJECTIVES: Cancer has been investigated using various pre-targeting techniques or models focusing on radiobombesin analogues; however, both are not offered together. In this study, nano-bombesin labeling by a pre-targeting system was undertaken to develop an alternative approach for prostate tumor treatment. METHODS: A two-step pre-targeting system utilizing a combination of streptavidin (SA), biotinylated morpholino (B-MORF), biotinylated BBN (B-BBN) with two different spacers (b-Ala and PEG), and a radiolabeled cMORF was evaluated in vitro and in vivo. RESULTS: Final conjugation conditions consisted of a 1:1:2 ratio of SA:B-MORF:B-BBN, followed by addition of 99mTc-cMORF to compensate for free MORF. In vitro binding experiments with prostate cancer cells (PC-3) revealed that total binding was time-dependent for the Ala spacer but not for the PEG spacer. The highest accumulation (5.06 ± 1.98 percent) was achieved with 1 hour of incubation, decreasing as time progressed. Specific binding fell to 1.05 ± 0.35 percent. The pre-targeting biodistribution in healthy Swiss mice was measured at different time points, with the best responses observed for 7-h and 15-h incubations. The effector, 99mTc-MAG3-cMORF, was administered 2 h later. Strong kidney excretion was always documented. The greatest tumor uptake was 2.58 ± 0.59 percentID/g at 7 h for B-bAla-BBN, with a region of interest (ROI) value of 3.9 percent during imaging. The tumor/blood ratio was low due to the slow blood clearance; however, the tumor/muscle ratio was 5.95. CONCLUSIONS: The pre-targeting approach with a peptide was a viable concept. Further evaluation with modified sequences of MORF, including less cytosine, and additional test intervals could be worthwhile.
Assuntos
Animais , Masculino , Camundongos , Bombesina/metabolismo , Imagem Molecular/métodos , Morfolinas/farmacocinética , Nanopartículas , Neoplasias da Próstata/metabolismo , Radioisótopos , Estreptavidina/farmacocinética , Bombesina/análogos & derivados , Bombesina , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão/métodos , Modelos Animais de Doenças , Camundongos Nus , Compostos de Organotecnécio , Neoplasias da Próstata , Distribuição Aleatória , Radioisótopos/química , Fatores de TempoRESUMO
Iranian scorpions belong mainly to the Buthidae and Scorpionidae families, distributed into 16 genera and 25 species. In Iran, similar to other parts of the world, there are a few known species of scorpions responsible for severe envenoming; amongst which Mesobuthus eupeus is the most common. Its venom contains several toxin fractions that may affect the ion channel. In the present study purification, labeling and biological evaluation of M. eupeus venom are described. For separation, soluble venom was loaded on a chromatography column packed with Sephadex G-50 gel. Subsequently, the fractions were collected according to UV absorption at a wavelength of 280 nm. Toxic fraction (F3) was loaded on an anionic ion exchanger resin and then on a cationic resin. Finally, toxic subfractions F3.1.6 and F3.1.9 were labeled with 99mTc and injected into normal mice to distinguish excretion pathway. The venom toxic fraction was successfully obtained in its purified form. Radiolabeling of toxic fractions was performed at high specific activity with radiochemical purity of more than 97 and 95% respectively for F3.1.6 and F3.1.9. Biodistribution studies in normal mice with two toxic fractions usually show rapid clearance of the compounds from blood and tissue except for kidneys. Since tissue distribution studies are very important for clinical purpose, the present findings suggest that 99mTc labeling of venom is a useful tool for in vivo studies and comprises an excellent approach to monitoring the process of biodistribution and kinetics of toxins.(AU)
Assuntos
Animais , Venenos/análise , Venenos de Escorpião/toxicidade , Cromatografia , ExfoliatinasRESUMO
Iranian scorpions belong mainly to the Buthidae and Scorpionidae families, distributed into 16 genera and 25 species. In Iran, similar to other parts of the world, there are a few known species of scorpions responsible for severe envenoming; amongst which Mesobuthus eupeus is the most common. Its venom contains several toxin fractions that may affect the ion channel. In the present study purification, labeling and biological evaluation of M. eupeus venom are described. For separation, soluble venom was loaded on a chromatography column packed with Sephadex G-50 gel. Subsequently, the fractions were collected according to UV absorption at a wavelength of 280 nm. Toxic fraction (F3) was loaded on an anionic ion exchanger resin and then on a cationic resin. Finally, toxic subfractions F3.1.6 and F3.1.9 were labeled with 99mTc and injected into normal mice to distinguish excretion pathway. The venom toxic fraction was successfully obtained in its purified form. Radiolabeling of toxic fractions was performed at high specific activity with radiochemical purity of more than 97 and 95 percent respectively for F3.1.6 and F3.1.9. Biodistribution studies in normal mice with two toxic fractions usually show rapid clearance of the compounds from blood and tissue except for kidneys. Since tissue distribution studies are very important for clinical purpose, the present findings suggest that 99mTc labeling of venom is a useful tool for in vivo studies and comprises an excellent approach to monitoring the process of biodistribution and kinetics of toxins.(AU)
Assuntos
Animais , Venenos de Escorpião/isolamento & purificação , Produtos Biológicos , Cromatografia , EscorpiõesRESUMO
The influence (in vivo and in vitro) of an Uncaria tomentosa extract (Cats claw) on the labeling of red blood cells (RBCs) and plasma and cellular proteins with technetium-99m (Tc-99m) was evaluated. For the in vivo treatment, animals were treated with Cats claw. For the in vitro treatment, heparinized blood was incubated with Cats claw before the addition of stannous chloride (SnCl2) and Tc-99m. Samples of plasma (P) and RBCs were separated and also precipitated with trichloroacetic acid. The soluble and insoluble fractions of P and RBCs were isolated. The analysis of the results of the in vivo study, indicates that there is no significant alteration on the uptake of Tc-99m by the blood constituents, but it significantly decrease (p<0.05) the labeling of blood constituents by in vitro methods. These effects could be due to chelation of stannous and /or pertechnetate ions and blockage of the Tc-99m bindings sites.
O objetivo do presente estudo foi avaliar a influência (in vivo e in vitro) de um extrato de Uncaria tomentosa (unha de gato) na marcação de hemácias e proteínas plasmáticas e celulares com tecnécio-99m (Tc-99m). Para o estudo in vivo, animais foram tratados com um extrato de unha de gato. Para o estudo in vitro, sangue heparinizado foi incubado com o extrato de unha de gato antes da adição de cloreto estanoso (SnCl2) e Tc-99m. Amostras de plasma e células foram separadas e também precipitadas com ácido tricloracético. As frações solúveis e insolúveis foram isoladas. A análise dos resultados do estudo in vivo, indica que não houve alteração significante na captação de Tc-99m pelos constituintes sanguíneos, entretanto, no tratamento in vitro, ocorreu redução significante da marcação de constituintes sanguíneos. Esses efeitos poderiam ser justificados por quelação dos íons estanoso e pertecnetato e bloqueio dos sítios de ligação do Tc-99m.
RESUMO
Aptamers, short, single stranded oligonucleotide entities, have been developed in the past 15 years against a plethora of targets and for a variety of applications. These range from inhibition of receptors and enzymes to the identification of small molecules in sensor applications, and from the development of targeted therapeutic to the design of novel diagnostic and imaging agents. Furthermore, aptamers have been designed for targets that cover a wide range of diseases, from HIV to tropical diseases, cancer and inflammation. Their easy development and flexibility of use and manipulation, offers further potential. In this paper we review their selection and consider some of the recent applications of aptamers in the design of radiopharmaceuticals for the targeted radiotherapy and medical imaging of disease.
Aptâmeros são pequenos oligonucleotídeos de cadeia simples, que têm sido desenvolvidos nos últimos 15 anos para diversos alvos e com várias aplicações. Essas incluem a inibição de receptores e enzimas, para a identificação de pequenas moléculas "sensoras" e o desenvolvimento de alvos terapêuticos para diagnóstico e imagem. Além disso, aptâmeros também foram desenvolvidos para alvos que incluem diferentes doenças, tais como HIV, doenças tropicais, câncer e inflamação. O fácil desenvolvimento, flexibilidade de uso e manipulação sugere outras aplicações potenciais. Esta revisão apresenta uma seleção de trabalhos e considera alguns dos mais recentes usos dos aptâmeros para o desenvolvimento de radiofármacos para radioterapia e diagnóstico por imagens.