Radiofármacos são compostos radioativos que podem ser usados tanto para diagnóstico como para terapia. O radiofármaco 99m-Tc-MIBI é a formação de um complexo contendo o radionúclideo Tecnécium-99m e seis moléculas de Sestamibi, usado principalmente para cintilografias do miocárdio, sendo o procedimento mais realizado dentro da medicina nuclear, por consequência, o radiofármaco mais comercializado. Já o radiofármaco 99m-Tc-DTPA é composto também pelo mesmo radioisótopo e por uma molécula de ácido pentético, a qual tem característica de um quelante com afinidade pelos rins, por isso, é possível fazer avaliação do sistema renal. Como os radiofármacos são considerados medicamentos, estão sujeitos às mesmas normativas, logo o objetivo deste trabalho foi desenvolver metodologia de doseamento destes insumos ativos antes da complexação com o radionuclídeo através da metodologia de Cromatografia Líquida de Alta Eficiência (CLAE). Dois métodos simples e eficientes foram desenvolvidos e validados para o MIBI em produto acabado e para a matéria-prima ácido pentético (DTPA), utilizando-se misturas de solvente orgânico e tampão. Os parâmetros de validação foram avaliados, obtendo resultados satisfatórios. Um teste de estabilidade para o radiofármaco MIBI em solução foi realizado e o resultado indicou uma preservação das características de aproximadamente 60 dias, e quando liofilizado de mais de 12 meses. Sendo assim, os métodos propostos foram considerados adequados para utilização na rotina da indústria farmacêutica. Como perspectivas, novas condições serão testadas para obter método de quantificação para o radiofármaco 99m-Tc-DTPA em produto acabado. / Radiopharmaceuticals are radioactive compounds that can be used for diagnostic and therapeutic purposes. Technetium (99mTc) sestamibi is a radiopharmaceutical including a coordination complex consisting of the radioisotope technetium-99m bound to six Sestamibi ligands, which is mainly used to image the myocardium via scintigraphy. This is the most common nuclear medicine procedure, making Technetium (99mTc) sestamibi the most commercialized radiopharmaceutical. Technetium (99mTC)-DTPA in turn is composed by the same radioisotope plus a molecule of Pentetic Acid, which, by its chelating properties, is used to scan renal system. As radiopharmaceuticals are regarded as drugs, they are subject to the same regulations; therefore, the objective of this study is to develop quantification methodology for these both active pharmaceutical ingredients before their complexation with the radioisotope by employing high-performance liquid chromatography (HPLC) methodology. Two simple, efficient methods were developed and validated for Sestamibi at its final form as well as for DTPA's raw material by using buffer and organic solvent mixtures. The validation parameters were evaluated with satisfactory results. A stability test was carried out for Sestamibi, indicating the preservation of characteristics for nearly 60 days, and for over 12 months when at its freezedryed form. The proposed methods were thus considered adequate for pharmaceutical industries. As perspectives, new conditions shall be tested to obtain a quantification method for Technetium (99mTC)-DTPA at its final form.

Submitted by Nathália Faria da Silva (nathaliafsilva.ufv@gmail.com) on 2017-06-19T17:19:11Z No. of bitstreams: 1 texto completo.pdf: 171277 bytes, checksum: 6352885a7289ac3d3dd61d7e80b3aa5e (MD5) / Made available in DSpace on 2017-06-19T17:19:11Z (GMT). No. of bitstreams: 1 texto completo.pdf: 171277 bytes, checksum: 6352885a7289ac3d3dd61d7e80b3aa5e (MD5) Previous issue date: 1997-06-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Em experimento conduzido em casa de vegetação, objetivou-se avaliar a eficiência dos extratores Mehlich-1, Mehlich-3 e DTPA quanto à disponibilidade de zinco em solos de Minas Gerais, com características químicas e físicas variáveis, na ausência e presença de calagem. Os tratamentos foram arranjados em esquema fatorial 7x2x5, correspondendo a sete solos, dois níveis de calagem e cinco doses de zinco, no delineamento em blocos casualizados, com três repetições. Amostras de 2dm 3 foram incubadas com e sem adição de calcário. As quantidades de calcário adicionadas foram determinadas por meio de curvas de neutralização da acidez, objetivando alcançar pH6,0. Após esse período de incubação, as amostras receberam zinco nas doses de 0, 2, 4, 6 e 8mgdm -3 , na forma de ZnSO 4 . Nessa mesma oportunidade, realizou-se adubação básica, sem zinco, com todos os outros macro e micronutrientes. Após 15 dias da fertilização das amostras, foram retiradas subamostras de 0,4 dm 3 , para avaliação de zinco pelos extratores Mehlich-1, utilizando filtragem logo após extração (M-1f) e retirada de alíquota após 16 horas (M-1s), Mehlich-3 (M-3) e DTPA-TEA. O volume de solo restante foi acondicionado em vasos plásticos para o cultivo do milho. Aos cinqüenta dias de cultivo foi analisada a produção de massa de matéria seca, bem como o teor e o conteúdo de zinco na parte aérea das plantas. Para avaliação da capacidade de extração dos diferentes métodos, foram ajustadas equações de regressão do Zn recuperado em função das doses adicionadas, para cada solo, nos dois níveis de calagem. Essas equações foram comparadas mediante teste de identidade de modelos, para avaliar a sensibilidade dos extratores à calagem. A resposta da planta à calagem e às doses de zinco foi avaliada pela produção de massa de matéria seca, teor e conteúdo de zinco na parte aérea. A capacidade de extração variou na seguinte ordem: M-1s>M-1f>M-3> DTPA, para todos os solos, na ausência e na presença de calagem. Os extratores M-1s e M-3 não apresentaram diferenças na capacidade de extração com a calagem, enquanto o M-1f e DTPA foram sensíveis à calagem. Os teores de zinco obtidos por todos os extratores correlacionaram-se significativa (p<0,05) e negativamente com o teor de argila e água retida a -33kPa dos solos, tanto na ausência como na presença de calagem. A capacidade de extração do DTPA apresentou-se melhor correlacionada com todas as características de solo, na presença de calagem, indicando que esse extrator pode ser melhor utilizado em solos com maiores valores de pH. Todos os extratores apresentaram correlações significativas (p<0,001) com o conteúdo de zinco na planta, podendo ser utilizados na avaliação da disponibilidade de zinco do solo. As plantas de milho apresentaram diminuição significativa na absorção de zinco com a calagem, sem contudo haver diminuição de produção, uma vez que, com a calagem, as plantas aumentaram a eficiência de utilização do nutriente. / This experiment was carried out under greenhouse conditions in order to evaluate the efficiency of Mehlich-1, Mehlich-3 and DTPA extractors for zinc availability in soils of Minas Gerais State presenting chemical and physical characteristics variable in the presence and absence of liming. Treatments were arranged in a 7x2x5 factorial scheme corresponding to seven soils, two liming levels and five zinc doses in a randomized block design with three replicates. The 2dm 3 samples were incubated with and without adding calcareous. The amounts of the added calcareous were determined by the acidity neutralization curves, aiming to attain pH6.0. After this incubation period, the samples were added zinc at the dosages of 0, 2, 4, 6 and 8mgdm -3 in the ZnSO 4 form. At this time, the basic adubation was realized without zinc and with all others macro and micronutrients. Fifteen days after sample fertilization, the 0.4dm 3 subsamples were removed for zinc evaluation by the Mehlich-1 extractors, using filtration just after extraction (M-1f) and removal of the aliquot 16 hours later (M-1s), Mehlich-3 (M-3) and DTPA-TEA. The remaining soil xvolume was conditioned in plastic pots for maize cropping. At fifty days cropping, the production of the dry matter mass was analyzed and the zinc concentration and content in the plant aerial part as well. To evaluate the extraction capacity of the different methods, the regression equations of the recovered Zn were adjusted as a function of the added doses, to each soil, in the two liming levels. These equations were compared through the model identity test in order to evaluate the extractor sensibility to liming. The plant response to both liming and Zn doses was evaluated by the production of dry matter mass, Zn concentration and content in the aerial part. The extraction capacity varied on the following order: M-1s>M-1f>M-3> DTPA, for all soils, in the presence and absence of liming. The extractors M-1s and M-3 didn’t present differences in the extraction capacity with liming, whereas M-1f and DTPA were liming-sensible. The Zn contents obtained by all extractors showed a significative (p<0.05) and negative correlation with the concentration of clay and water retained at -33kPa of the soils, in the absence as in the presence of liming. The DTPA extraction capacity correlated better with all soil characteristics, in the liming presence, indicating that this extractor can be better used in those soils with higher pH values. All extractors presented significative correlations (p<0.001) with the Zn content in plant, and can be used in evaluating Zn availability in the soil. The maize plants presented a significative decrease in absorbing zinc with the liming; however the yield didn’t diminished, since the plants increased their nutrient utilization efficiency with liming.

Radiofármacos são compostos radioativos que podem ser usados tanto para diagnóstico como para terapia. O radiofármaco 99m-Tc-MIBI é a formação de um complexo contendo o radionúclideo Tecnécium-99m e seis moléculas de Sestamibi, usado principalmente para cintilografias do miocárdio, sendo o procedimento mais realizado dentro da medicina nuclear, por consequência, o radiofármaco mais comercializado. Já o radiofármaco 99m-Tc-DTPA é composto também pelo mesmo radioisótopo e por uma molécula de ácido pentético, a qual tem característica de um quelante com afinidade pelos rins, por isso, é possível fazer avaliação do sistema renal. Como os radiofármacos são considerados medicamentos, estão sujeitos às mesmas normativas, logo o objetivo deste trabalho foi desenvolver metodologia de doseamento destes insumos ativos antes da complexação com o radionuclídeo através da metodologia de Cromatografia Líquida de Alta Eficiência (CLAE). Dois métodos simples e eficientes foram desenvolvidos e validados para o MIBI em produto acabado e para a matéria-prima ácido pentético (DTPA), utilizando-se misturas de solvente orgânico e tampão. Os parâmetros de validação foram avaliados, obtendo resultados satisfatórios. Um teste de estabilidade para o radiofármaco MIBI em solução foi realizado e o resultado indicou uma preservação das características de aproximadamente 60 dias, e quando liofilizado de mais de 12 meses. Sendo assim, os métodos propostos foram considerados adequados para utilização na rotina da indústria farmacêutica. Como perspectivas, novas condições serão testadas para obter método de quantificação para o radiofármaco 99m-Tc-DTPA em produto acabado. / Radiopharmaceuticals are radioactive compounds that can be used for diagnostic and therapeutic purposes. Technetium (99mTc) sestamibi is a radiopharmaceutical including a coordination complex consisting of the radioisotope technetium-99m bound to six Sestamibi ligands, which is mainly used to image the myocardium via scintigraphy. This is the most common nuclear medicine procedure, making Technetium (99mTc) sestamibi the most commercialized radiopharmaceutical. Technetium (99mTC)-DTPA in turn is composed by the same radioisotope plus a molecule of Pentetic Acid, which, by its chelating properties, is used to scan renal system. As radiopharmaceuticals are regarded as drugs, they are subject to the same regulations; therefore, the objective of this study is to develop quantification methodology for these both active pharmaceutical ingredients before their complexation with the radioisotope by employing high-performance liquid chromatography (HPLC) methodology. Two simple, efficient methods were developed and validated for Sestamibi at its final form as well as for DTPA's raw material by using buffer and organic solvent mixtures. The validation parameters were evaluated with satisfactory results. A stability test was carried out for Sestamibi, indicating the preservation of characteristics for nearly 60 days, and for over 12 months when at its freezedryed form. The proposed methods were thus considered adequate for pharmaceutical industries. As perspectives, new conditions shall be tested to obtain a quantification method for Technetium (99mTC)-DTPA at its final form.

Made available in DSpace on 2014-06-12T15:54:59Z (GMT). No. of bitstreams: 2 arquivo6200_1.pdf: 4199376 bytes, checksum: 5a46d3d2af28d10ea5aec5bc448e129b (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2003 / A manobra de sustentação máxima da inspiração (SMI) é utilizada para melhorar a ventilação através de inspirômetros de incentivos (II). O breath-stacking (BS) técnica alternativa ao II não necessita da cooperação do paciente. Os objetivos deste estudo foram analisar o padrão regional de deposição pulmonar, usando as técnicas de BS e II e correlacionar o volume máximo alcançado com o índice de deposição (ID) do radioaerossol. Foram estudados 18 voluntários, saudáveis, com idade de 22,72±2,96 no Instituto de Medicina Nuclear de Fortaleza e na Faculdade Integrada do Ceará. Foram medidos o volume pulmonar alcançado e a captação das imagens cintilográficas, durante as técnicas. O radioaerossol utilizado foi o 99mTc-DTPA. Após a inalação, foram obtidas imagens na câmara de cintilação. Foi realizada uma medida cintilográfica em respiração espontânea, considerada imagem-controle (C). Foram delimitadas regiões de interesse (ROIS) e analisados o ID nos gradientes vertical e horizontal. Para análise estatística, utilizou-se ANOVA, teste t-Student pareado e correlação de Pearson. Para o grupo total, o II favoreceu a deposição em terço médio(p=0,03) e região central(p<0,001) e o BS em inferior(p=0,03) e periférica(p<0,001). No masculino, a deposição em terço superior(p=0,04) foi favorecida pelo II. Não houve correlação entre o volume alcançado e a deposição durante BS e II, nem alteração no volume pulmonar alcançado durante as técnicas. Os resultados sugerem que a técnica de II proporciona um padrão regional de deposição do radioaerossol em vias aéreas centrais, enquanto a BS em vias aéreas de pequeno calibre

Memoria para optar al Título Profesional de Ingeniero en Recursos Naturales Renovables

Abstract The purpose of the current study was to evaluate the intercorrelations of magnetic resonance imaging (MRI) findings and clinical symptoms and signs in sciatic patients. Furthermore, determinants of spontaneous HNP resorption and the effect of anti-inflammatory treatments (periradicular methylprednisolone injection and intravenous infliximab) on spontaneous HNP resorption were evaluated. MRI follow-up was performed at baseline, after two months, after six months and after one-year for patients with unilateral sciatica to evaluate determinants of spontaneous HNP resorption and the effect of periradicular methylprednisolone injection on spontaneous HNP resorption. At baseline the study population consisted of 160 patients (group A). MRI follow-up for 21 patients with unilateral sciatica was performed at baseline and after two weeks, after three months and after six months to evaluate the effect of infliximab, a monoclonal TNFα antagonist, infusion on spontaneous HNP resorption (group B). Patients in group A were randomized to receive either periradicular saline or methylprednisolone. Volume of HNP, extent and thickness of enhancement (in Gd-DTPA MRI) and degree of disc displacement were measured and the symptoms and signs were followed repeatedly. The extent of rim enhancement correlated significantly with the degree of disc displacement. The duration of sciatic symptoms correlated negatively with enhancement parameters. The clinical symptoms did not correlate significantly with the different enhancement parameters or disc herniation volume. Achilles reflex abnormality correlated significantly with all enhancement parameters for lesions at L5-S1. Significant decrease in HNP volume occurred from baseline to two moths, and even more so during the whole one year follow-up period. Higher baseline scores of rim enhancement thickness, higher degree of HNP displacement in the Komori classification and age category of 41–50 years were associated with a higher resorption rate. Clinical symptoms alleviation occurred concordantly with a faster resorption rate. No significant difference was noted in the decrease of HNP volume in the saline and methylprednisolone injection groups in follow-up imaging during one year. The enhancement parameters (thickness and extent of rim enhancement) did not differ significantly in the different treatment groups. In group B, 11 patients received intravenous infliximab and 10 saline. Baseline demographic data, pain scores, and clinical status, did not differ between the treatment groups. HNP volume decreased significantly in both groups (P &lt; 0.01). There was no significant difference in HNP volume changes between the treatment groups. By two weeks, enhancement thickness increased significantly in the infliximab compared placebo group (p=0.003). Two patients in each group required back surgery prior to the 6-month assessment.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Klaudia Sabolová Supervisor: Mgr. Pavel Bárta, Ph.D. Title of diploma thesis: The preparation and the following in vitro saturation study of the radiopharmaceutical 99m Tc-DTPA-ramucirumab on PC-3 cell line In cancer treatment, immunology is given prominence, which compared with chemotherapy and radiotherapy has a lower risk of side effects on healthy tissues. Immunotherapy includes application of monoclonal antibodies aimed at some tumour antigens using either non conjugated monoclonal antibodies or conjugated ones with an appropriate effector element, such as radionuclide. Angiogenesis plays the important role in pathogenesis of tumour diseases. Angiogenic process is regulated mostly by the interactions among vascular growth factors (VEGFs) and VEGF receptors (VEGFR). The main regulator of angiogenesis is VEGF-A. The blocking of the interaction among VEGF-A and its receptors VEGFR-1 and VEGFR-2 inhibits angiogenesis, and so does the growth of tumours. Ramucirumab is the monoclonal antibody with antiangiogenic effect, which blocks this interaction by its binding to the extracellular VEGFR-2 domain with high affinity. The presented study is focused on ramucirumab...

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20083号 / 医博第4176号 / 新制||医||1018(附属図書館) / 33199 / 京都大学大学院医学研究科医学専攻 / (主査)教授 増永 慎一郎, 教授 妹尾 浩, 教授 松田 道行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Pressurized hot water and DTPA-Sorbitol are two relatively new soil boron (B) extraction methods with potential to replace the cumbersome hot water extraction. The objective of this research is to produce data in support of acceptance or rejection of these two alternative B extractions. The three soil tests were used to extract B from samples of calcareous sand and silt loam and limed, loamy fine sand treated with 10 levels of B and incubated for 7 and 28 d. As B application increased so did extractable B with each extraction method. High correlations (r of 0.977 to 0.999) were observed between extractable B and rate of B application with all three methods. Hot water generally extracted the least and pressurized hot water the most B regardless of soil type, rate of application or duration of incubation. Greenhouse and field experiments were conducted on one limed acid and two alkaline soils naturally low in B to test alfalfa response to B fertilizer. Values from the three soil extraction methods were correlated to yield, B tissue concentration and total B removal of alfalfa. In greenhouse studies with varying levels of soil applied B, highly significant relationships exist between extractable soil B and both tissue B concentration and total B removal. Correlations between yield and extractable soil B were impossible to obtain because of a lack of alfalfa yield responses to applied boron. All three methods accurately predict plant B tissue concentrations and total B removal. The field experiment produced a significant positive relationship between total alfalfa yield and extractable B using hot water and pressurized hot water extractions, but not using DTPA-Sorbitol. The results observed in this research support pressurized hot water extraction as the better of the two alternatives to replace hot water extraction in a broad range of soil types.

L’acquisition de données structurales et thermodynamiques relatives à des systèmes actinides (An(III), Pu(IV) Pa(V))–acides organiques polyfonctionnels (citrique, NTA, DTPA), en solution aqueuse, vise à une meilleure compréhension des interactions actinides-ligands essentielle à l’optimisation de procédés de séparation, de décorporation, et également à l’évaluation de la sûreté des sites de stockage de déchets radioactifs. Le comportement du protactinium pentavalent à l’échelle des traces en présence des anions citrates et NTA a fait l’objet d’études systématiques par extraction liquide-liquide dans le système TTA/Toluène/HClO₄/NaClO₄/Pa(V)/ligands. Après avoir déterminé l’ordre limite des complexes (3 pour Pa(V)-Cit et 2 pour Pa(V)-NTA), les constantes de formation associées à chaque espèce ont pu être calculées. L’étude multi-technique (électrophorèse capillaire et spectrofluométrie laser) sur la complexation des An(III) par le DTPA, réalisée à plusieurs pH, a permis de mettre en évidence la coexistence des complexes mono-protoné (AnHDTPA–) et déprotoné. (AnDTPA²–) pour des solutions acides et faiblement acides. Une réinterprétation des données de la littérature, en considérant les deux complexes, a permis de faire converger les valeurs des constantes de complexation des espèces qui étaient jusqu’à maintenant dispersées. L’étude thermodynamique a ensuite été complétée par une étude théorique (calculs DFT). La structure des complexes protoné et non protoné et le mode de coordination du Curium ont ainsi été établis. L’étude exploratoire sur la complexation du Pu(IV) par le DTPA dans des conditions de pH proches du milieu biologique a nécessité le développement d’un protocole expérimental en trois étapes : protection de Pu(IV) contre l’hydrolyse avec NTA (pH faible), augmentation du pH vers des conditions neutres, compétition entre la complexation de Pu(IV) par le NTA et le DTPA. Les expériences préliminaires réalisées entre pH 1,5 et 3,5 par électrophorèse capillaire (EC-ICP-MS), semblent indiquer l’existence d’effet cinétique ou/et l’existence d’un complexe mixte. Les interprétations faites lors de cette étude exploratoire sont à confirmer. / A thorough knowledge of the chemical properties of actinides is now required in a wide variety of fields: extraction processes involved in spent fuel reprocessing, groundwater in the vicinity of radioactive waste packages, environmental and biological media in the case of accidental release of radionuclides. In this context, the present work has been focused on the complexation of Am(III), Cm(III), Cf(III), Pu(IV) and Pa(V) with organic ligands: DTPA, NTA and citric acid. The complexation of pentavalent protactinium with citric and nitrilotriacetic acids was studied using liquid-liquid extraction with the element at tracer scale (CPa < 10-10M). The order and the mean charge of each complex were determined from the analysis of the systematic variations of the distribution coefficient of Pa(V) as function of ligand and proton concentration. Then, the apparent formation constants related of the so-identified complexes were calculated. The complexation of trivalent actinides with DTPA was studied by fluorescence spectroscopy (TRLFS) and capillary electrophoresis (CE-ICP-MS). The coexistence of the mono-protonated and non-protonated complexes (AnHDTPA– and AnDTPA²–) in acidic media (1.5 ≤ pH ≤ 3.5) was shown unambiguously. Literature data have been reinterpreted by taking into account both complexes and a consistent set of formation constants of An(III)-DTPA has been obtained. The experimental study was completed by theoretical calculations (DFT) on Cm-DTPA system. The coordination geometry of Cm in CmDTPA²- and CmHDTPA- including water molecules in the first coordination sphere has been determined as well as interatomic distances. Finally, a study on the complexation of Pu(IV) with DTPA was initiated in order to more closely mimic physiological conditions. A three-step approach was proposed to avoid plutonium hydrolysis: i/ complexation of Pu(IV) with (NTA) in order to protect Pu(IV) from hydrolysis (at low pH) ii/ increase of pH toward neutral conditions and iii/ competition between the complexation of Pu with NTA and with DTPA. The preliminary experiments performed with CE-ICP-MS in the pH range 1.5 - 3.5 tend to indicate kinetic effect or/and the presence of mixed complex.