Synthesis, quality control and dosimetry of the radiopharmaceutical 18F-sodium fluoride produced at the Center for Development of Nuclear Technology - CDTN / Síntese, controle de qualidade e dosimetria do radiofármaco 18 -F de fluoreto de sódio produzido no Centro de Desenvolvimento da Tecnologia Nuclear - CDTN

18F-Sodium fluoride (Na18F) is a radiopharmaceutical used for diagnosis in nuclear medicine by positron emission tomography (PET) imaging. Bone scintigraphy is normally performed using 99mTc-MDP. However, 18F PET scans promise high quality imaging with increased resolution and improved sensitivity and specificity. In order to make available a tool for more specific studies of tumors and non-oncological diseases of bone tissue, the UPPR/CDTN team undertook the production and quality control of Na18F injectable solution with the physical-chemical, microbiological and biological characteristics recommended in the U.S. Pharmacopeia. Na18F radiochemical purity was 96.7 ± 1.3 percent, with Rf= 0.026 ± 0.006. The product presented a pH of 5.3 ± 0.6, half life of 109.0 ± 0.8 minutes, endotoxin limit < 5.0 EU.mL-1 and no microbial contaminants. The biodistribution of Na18F was similar to that described in the literature, with a clearance of 0.19 mL.min-1 and distribution volume of 18.76 mL. The highest bone concentration (5.0 ± 0.5 percentID.g-1) was observed 20 minutes after injection. Na18F produced at the UPPR presented all the quality assurance requirements of the U.S. Pharmacopeia and can be safely used for clinical bone imaging.

O Fluoreto de sódio 18F (Na18F) é um radiofármaco empregado para diagnóstico através da Tomografia por Emissão de Pósitrons (PET). Cintilografias ósseas são normalmente obtidas utilizando-se 99mTc-MDP. Entretanto, o interesse pelo Na18F é crescente, principalmente devido à obtanção de imagens de elevada resolução. Com o objetivo de tornar disponível uma ferramenta mais específica para estudos de tumores e doenças não-oncológicas do tecido ósseo, o grupo da UPPR/CDTN implementou a produção e o controle de qualidade da solução injetável de Na18F com as características físico-química, microbiológica e biológica preconizadas pela farmacopéia. Sua pureza radioquímica foi de 96,7 ± 1,3 por cento, com Rf= 0,026 ± 0,006. O produto apresentou pH igual a 5,3 ± 0,6, tempo de meia-vida de 109,0 ± 0,8 minutos, limite de endotoxinas < 5,0 EU.mL-1 e ausência de microrganismos. O perfil de biodistribuição em camundongos foi semelhante ao disponível na literatura, com depuração igual a 0,19 mL.min-1 e volume de distribuição igual a 18,76 mL. A concentração máxima (5,0 ± 0,5 por cento DI.g-1) foi observada no osso 20 minutos após a injeção. O Na18F produzido na UPPR do CDTN apresentou os parâmetros de qualidade definidos na farmacopéia americana e pode ser usado com segurança para uso clínico em cintilografia óssea.

Organotin(IV) complexes of 2-pyridineformamide-derived thiosemicarbazones: antimicrobial and cytotoxic effects.

Reaction of n-butyltin trichloride [(n-Bu)SnCl(3)] with 2-pyridineformamide thiosemicarbazone (H2Am4DH) and its N(4)-methyl (H2Am4Me) and N(4)-ethyl (H2Am4Et) derivatives gave [(n-Bu)Sn(2Am4DH)Cl(2)] (1), [(n-Bu)Sn(2Am4Me)Cl(2)] (2), and [(n-Bu)Sn(2Am4Et)Cl(2)] (3). Thiosemicarbazones as well as their tin complexes are active as antimicrobials against the growth of Candida albicans and Salmonella typhimurium and were highly active against malignant glioblastoma. The cytotoxic activity of complexes 1-3 is similar. Among the studied compounds [(n-Bu)Sn(2Am4DH)Cl(2)] (1) was the most active as antiproliferative (cytostatic) agent. Thiosemicarbazones and their tin(IV) complexes proved to be more potent as cytotoxic agents than cisplatin. All the compounds were able to induce apoptosis.

Phoneutria nigriventer omega-Phonetoxin IIA: a new tool for anti-calcium channel autoantibody assays in Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is a neurological autoimmune disease in which downregulation of voltage-gated calcium channels (VGCCs) leads to reduced acetylcholine release from motoneuron terminals. 70% of cases are paraneoplastic and rapid diagnosis of LEMS can result in early detection of the underlying tumor. Serological assays based on the capacity of autoantibodies to precipitate VGCCs labeled with radioligands provide valuable data. We have established a novel assay using the spider venom peptide 125I-omega-Phonetoxin IIA (125I-omegaPtxIIA). 125I-omegaPtxIIA labeled recombinant Cav2.1 and Cav2.2 channels and endogenous VGCCs in rat brain membranes. Autoantibodies that immunoprecipitate a 125I-omegaPtxIIA/channel complex were detected in 26/31 (84%) LEMS patients. The patients that were seropositive in the 125I-omegaPtxIIA assay corresponded precisely to the population that was positive for Cav2.1 and/or Cav2.2 antibodies detected using two different omega-conotoxins. Thus, the 125I-omegaPtxIIA assay detects a broader spectrum of autoantibody specificities than current omega-conotoxin-based assays.

Preparation of crotalus venom radiolabeled with technetium-99m as a tool for biodistribution study

Technetium-99m (99mTc) has been the radionuclide of choice for nuclear medicine procedures and experimental research. Because of its optimal nuclear properties, 99mTc is suitable for high efficiency detection with the advantage of reduced radiological waste. Crotalus venom (CV) has been shown to reduce tumors in clinical studies and tissue distribution studies are very important for clinical use. The goal of this work was to obtain CV labeled with 99mTc which preserves its biological activity. After labeling, biological activity was assessed by hemolytic activity evaluation. Labeled and crude venom caused indirect hemolysis provided that the incubation medium contained an exogenous source of lecithin. High yield radiolabeled-CV was obtained and biological activity was preserved. The results suggest that 99mTc-CV can be a useful tool for biodistribution studies.

Tecnécio-99m tem sido o radioisótopo de escolha para procedimentos médicos e pesquisas experimentais. Em decorrência de suas propriedades nucleares, 99mTc é adequado para detecção de alta eficiência com a vantagem do baixo risco radiológico. O veneno de Crotalus (CV) apresentou propriedades antitumorais em estudos clínicos e estudos de biodistribuição são fundamentais em pesquisas clínicas. Esse trabalho teve como objetivo obter um análogo de veneno de Crotalus marcado com 99mTc que preservasse sua atividade biológica. Após a marcação, a atividade biológica foi avaliada através do ensaio de atividade hemolítica. Veneno nativo e marcado apresentaram atividade hemolítica indireta quando incubados em um meio contendo uma fonte exógena de lecitina. Obteve-se um alto rendimento de marcação e a atividade biológica das moléculas foi preservada. Nossos resultados sugerem que 99mTc-CV pode representar uma ferramenta muito útil para estudos de biodistribuição.

Effects of low-dose ionising radiation on pituitary adenoma: is there a role for L-type calcium channel?

Pituitary adenomas constitute about 6-18 percent of brain tumours in adults. Activation of voltage gated calcium currents can account for growth hormone oversecretion in some GH-secreting pituitary adenomas that produce an acromegaly appearance and increase mortality. Ca2+ ions, as mediators of intracellular signalling, are crucial for the development of apoptosis. However, the role of [Ca2+] in the development of apoptosis is ambiguous. In this study, the effects of low-dose ionising gamma radiation (60Co) on rat pituitary adenoma cells survival and proliferation and the role of calcium channels on the apoptosis radio-induced were evaluated. Doses as low as 3 Gy were found to inhibit GH3 cell proliferation. Even though there was a significant number of live cells,168 hours following irradiation, they were not able to proliferate. The results indicate that the blockade of extracellular calcium influx through these channels does not interfere in the radiation-induced apoptosis in GH3 cells.

Adenomas de pituitária constituem cerca de 6-18 por cento dos tumores cerebrais em adultos. A ativação de correntes de cálcio dependentes de voltagem podem levar à super-excreção de hormônio do crescimento produzindo acromegalia e aumentando a mortalidade. íons Ca2+ como mediadores de sinalização intracelular são cruciais no desenvolvimento da apoptose. No entanto, o papel da [Ca 2+] no desenvolvimento da apoptose é ambíguo. Neste estudo nós avaliamos os efeitos de baixas doses de radiação gama (60Co) na sobrevivência e proliferação de células de adenoma de pituitária de rato e o papel do cálcio na apoptose radio-induzida. Nossos resultados mostraram que a dose de 3Gy foi suficiente para inibir a proliferação das células GH3. Apesar de existir um número significativo de células vivas após 168 horas do tratamento com radiação, elas não estavam aptas a proliferar. Nossos resultados também indicaram que bloqueio do influxo de cálcio extracelular não interfere na apoptose induzida pela radiação.