Dissertations / Theses on the topic 'Re-188'

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Tese (Doutoramento)
IPEN/T
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

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Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Thesis (Ph. D.)--University of Missouri-Columbia, 1996.
"m in ⁹⁹mTc on short title page is supercript." Typescript. Vita. Includes bibliographical references (leaves 131-136). Also available on the Internet.

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Tese (Doutoramento)
IPEN/T
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Tecnécio-99m é o radionuclídeo mais utilizado em procedimentos para imagem diagnóstica na Medicina Nuclear, mais de 80 % dos radiofármacos são compostos marcados com 99mTc. 99mTc-DMSA(V) tem sido usado no diagnóstico de tumores de tecidos moles, cabeça e pescoço. Este radiofármaco tem uma alta especificidade para detecção de carcinoma medular de tireóide e metástase óssea em vários tipos de cânceres. Estudos de biodistribuição do 188Re-DMSA(V) tem mostrado que suas propriedades farmacocinéticas são similares ao do 99mTc-DMSA(V), então este agente poderia ser usado para terapia desses tumores. O objetivo desse trabalho é o desenvolvimento de métodos para marcação do DMSA(V) com 99mTc e 188Re. O 99mTc-DMSA(V) pode ser preparado por dois métodos. Um dos métodos é o método indireto, que é através do kit comercial de DMSA(III), ajustando-se o pH de 2,5 para ~8,5 com NaHCO3, que foi estudado e otimizado, apresentando bons rendimentos de marcação. O outro é o método direto, pelo preparo de um kit liofilizado de DMSA(V) pronto para marcação com 99mTc, sendo o método de interesse do trabalho pela maior praticidade no uso clínico. A formulação mais adequada do método direto foi: 1,71 mg de DMSA, 0,53 mg de SnCl2.2H2O e 0,83 mg de ácido ascórbico (pH 9). Marcando-se esse kit com 1 a 2 mL de 99mTc, com atividades de até 4736 MBq (128 mCi), e tempo instantâneo de reação, consegue-se rendimento de marcação maior que 95%. O kit liofilizado foi estável por até 6 meses e estudos de biodistribuição confirmaram a qualidade do DMSA (V) marcado com 99mTc usando este kit. O potencial de redução do Re é mais baixo do que do Tc, com isso as condições de preparação do 188Re-DMSA(V) são diferentes das usadas para o 99mTc-DMSA(V). O 188Re-DMSA(V) é preparado em meio ácido, com isso é possível utilizar o kit comercial de DMSA(III) para marcação com 99mTc, que apresenta pH 2,5, na preparação do 188Re- DMSA(V). Com este método conseguiu-se rendimentos de marcação superiores a 95%, com tempo de reação de 30 minutos à 100 ºC, utilizando no máximo 1 mL de 188ReO4 -. Outro método de preparação do 188Re-DMSA(V) também foi estudado, através de um kit líquido contendo 2,5 mg de DMSA, 1,00 mg de SnCl2.2H2O, 30 mg de oxalato de sódio e pH 5. Este kit marcado com 1 mL de 188ReO4 -, com 15 minutos de reação à temperatura ambiente apresentou rendimento de marcação de aproximadamente 91%.
Technetium-99m is the most useful radionuclide in diagnostic imaging procedures in Nuclear Medicine, more than 80 percent of radiopharmaceuticals are 99mTc-labeled compounds. 99mTc-DMSA(V) has been used for imaging of soft tissue, head and neck tumors. It shows a particularly high specificity for medullary thyroid carcinoma and bone metastases in a variety of cancers. Biodistribution studies of 188Re-DMSA(V) have shown that its general pharmacokinetic properties are similar to that of 99mTc-DMSA(V), so this agent could be used for targeted radiotherapy of these tumors. The aim of this work is the development of methods of labeling DMSA(V) with 99mTc and 188Re. 99mTc-DMSA(V) can be prepared by two methods. One of them is the indirect one, through the use of a commercial kit of DMSA (III), by adjusting the pH from 2.5 to ~8.5 with NaHCO3. This method was evaluated and optmized presenting high labeling yields. The other method is the direct one, through the preparation of a liophylised kit ready for labeling with 99mTc, being the method of interest of this work, due to the easy of its clinical use. The most adequate formulation of the kit was: 1.71mg of DMSA, 0.53mg of SnCl2.2H2O and 0.83 mg of ascorbic acid (pH 9). Labeling yields higher than 95% were achieved labeling this kit with 1 to 2 mL of 99mTc with activities up to 4736 MBq (128 mCi). The kit was stable up to 6 months and biodistribution studies confirmed the quality of the DMSA (V) labeled with 99mTc using this kit. The reduction potential of Re is lower than the one for Tc, so the labeling conditions of 188Re-DMSA(V) are diferent from the ones used for 99mTc- DMSA(V). 188Re-DMSA(V) is prepared in acid solution, that makes it possible to use the DMSA (III) comercial kit developed for labeling with 99mTc, prepared in pH 2.5, for labeling with 188Re. Labeling yields higher than 95% were achieved with this methodology, with a rection time of 30 minutes at 100oC using no more than 1 mL of 188ReO4 -. Another method of preparing 188Re-DMSA(V) was also evaluated, using a liquid kit containing 2.5mg of DMSA, 1.00mg of SnCl2.2H2O and 30mg of sodium oxalate at pH 5. This kit was labeled with 1 mL of 188ReO4 -, with 15 minutes of reaction at room temperature resulting in a labeling yield of about 91%.

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Dissertação (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

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Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

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Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Recently we have described the synthesis of a new class of asymmetrical nitrido complexes, based on the chemical properties of the substitution labile [Tc(N)X2(PNP)]2+ complex (PNP=aminodiphosphine, X=Cl, OH, H2O), which represent an interesting opportunity in design both perfusion and target-specific radiopharmaceuticals. According to this strategy, the strong electrophylic [Tc(N)(PNP)]2+ moiety efficiently reacts with bifunctional ligands (XY) carrying coordinating atoms π-donors such as S, O or N, to afford asymmetrical nitrido heterocomplexes of the type [Tc(N)(XY)(PNP)]0/+. In this work, studies to demonstrate the effective applicability of this technology to the preparation of perfusion and target-specific agents are reported, through synthesis and biological evaluation of: 1) 99mTc-nitrido complexes as potential myocardial imaging tracers, 2) 99mTc-nitrido complexes as potential target-specific agents, for imaging CCK-B receptor, 3) 188Re-nitrido complexes for therapeutic targeting.

Biologische Systeme sind in der Lage sich an eine Niedrig-Dosis-Bestrahlung anzupassen und eine geringere Sensitivität gegenüber einer nachfolgenden Hoch-Dosis-Bestrahlung zu entwickeln. Dieses Phänomen wird als adaptive Antwort bezeichnet und wurde nach der Bestrahlung mit externen Strahlungsquellen wiederholt in vivo und in vitro untersucht. Im Gegensatz dazu gibt es für die Bestrahlung mit offenen Radionukliden keine systematischen und vergleichenden Untersuchungen. Im Mittelpunkt dieser Arbeit standen der Nachweis sowie die Analyse der adaptiven Antwort an PC Cl3-Zellen nach Bestrahlung mit den offenen Radionukliden Re-188 und Tc-99m. Die Zellschädigung wurde mit dem alkalischen Komet-Assay, zur Bestimmung des initialen DNA-Schadens und dem Koloniebildungstest, zur Ermittlung des klonogenen Überlebens, untersucht. Zur Aufklärung von möglichen Regulationsmechanismen der adaptiven Antwort wurde die Induktion und Reparatur von DSB mit dem gamma-H2AX-Immunfluoreszenz-Assay und die intrazelluläre Radionuklidaufnahme betrachtet. In dieser Arbeit erfolgte erstmals eine systematische Untersuchung der adaptiven Antwort nach Bestrahlung mit offenen Radionukliden in vitro. Insgesamt zeigen diese Ergebnisse, dass nach Bestrahlung mit offenen Radionukliden eine adaptive Antwort ausgebildet wird. Diese ist von der Strahlenqualität während Vor- und Folgebestrahlung sowie der Art der DNA-Schädigung und den initiierten Reparaturprozessen abhängig. Weiter Einflussfaktoren sind die Erholungszeit, die Vorbestrahlung (Dosis, Strahlenqualität) und die Art des Schadensnachweises. Neben den bekannten Regulationsmechanismen wurde erstmals die Reduktion der intrazellulären Radionuklidaufnahme als weitere mögliche adaptive Antwort beschrieben.

Use of Re-Os systematics in sulfides from the Bagdad porphyry Cu-Mo deposit provide information on the timing of mineralization and the source of the ore -forming elements. Analyzed samples of pyrite, chalcopyrite and molybdenite mainly from the quartz monzonite and porphyritic quartz monzonite units are characterized by a moderate to strong potassic alteration (secondary biotite and K- feldspar). Rhenium concentrations in molybdenite are between 330 and 730 ppm. Two molybdenite samples from the quartz monzonite and porphyritic quartz monzonite provide a Re-Os isotope age of 71.7 ± 0.3 Ma. A third sample from a molybdenite vein in Precambrian rocks yields an age of 75.8 ± 0.4 Ma. These molybdenite ages support previous suggestions of two mineralization episodes in the Bagdad deposit. An early event at 76 Ma and a later episode at 72 Ma. Pyrite Os and Re concentrations range between 0.008-0.016 and 3.9-6.8 ppb, respectively. Chalcopyrite contains a wide range of Os (6 to 91 ppt) and Re (1.7 to 69 ppb) concentrations and variable ¹⁸⁷Os/¹⁸⁸Os ratios that range between 0.13 to 22.27. This variability in the chalcopyrite data may be attributed to different copper sources, one of them the Proterozoic volcanic massive sulfides in the district, or to alteration and remobilization of Re and Os. Analyses from two pyrite samples yield an eight point isochron with an age of 77 ± 15 Ma and an initial ¹⁸⁷Os/¹⁸⁸Os ratio of 2.12. This pyrite Re-Os isochron age is in good agreement with the molybdenite ages. We interpret the highly radiogenic initial 1870s/188Os as an indication that the source of Os and, by inference, the ore-forming elements for the Bagdad deposit, was mainly the crust. This conclusion agrees with previous Pb and Nd isotope studies and supports the notion that a significant part of the metals and magmas have a crustal source.

碩士
國立陽明大學
醫學生物技術研究所
87
Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. HCC is especially prevalent in South-east Asia, Japan and sub-Saharan Africa. In Taiwan HCC is the most common cancer in males and the second most common in females. The tumor often presents late, and surgery is difficult or impossible in most patients. Treatment of inoperable HCC with systemic cytotoxic chemotherapy has not been successful, with little or no improvement in the survival rate. The median survival time of patients with unresectable HCC may be as low as 4 month. Lipiodol, an iodinated ester derived from poppy-seed oil, has been found to be selectively retained in hepatic tumors. Transcatheter infusion of Lipiodol via the hepatic artery has been used increasingly for the detection and treatment of hepatic cancers. Even tiny malignant nodules have been detected by this method. The selective retention of Lipiodol in hepatic tumors suggests its potential as a carrier for chemotherapeutic or radiotherapeutic agents for targeted therapy purposes. In this study, we labeled Lipiodol with 188Re and analyzed its biodistribution in the hepatoma bearing rats following intra-hepatic arterial infusion. In the mean while to evaluate it’s optimal therapeutic effect. Our biodistribution data showed a high level of radioactivity retained in the hepatoma. The tumor to normal liver ratio was increased with time. The level of radioactivity in brain, bone marrow, and testis were relatively low. In safety test, Lipiodol was injected into the liver tissue via hepatic artery, a strong embolisation effect was observed after Lipiodol injection. This suggests that injection volume of Lipiodol is an important consideration in clinical practice. In the present study we used an In vivo-In vitro Soft Agar Colongenic Assay technique (SACA) to analyze the relationship between external radiation dose (2~30Gy) and internal radioactivity (0.5、1、2mCi/50μL) of Re-188 Lipiodol. The results demonstrated that 2mCi/50μL Re-188 Lipiodol administration was equivalent to about 18.6Gy of an external irradiation. This indicated a good tumor dose can be achieved by Re-188 Lipiodol injection. Microscopic and macroscopic observation of Re-188 Lipiodol in the hepatoma were studied using autoradiography, sudan stain, and γ-camera imaging techniques. It was found that Re-188 Lipiodol has accumulated specifically in the tumor 4 hours after intra-arterial injection. It was also noted that Re-188 Lipiodol was distributed to the normal liver tissues at earlier phase, then delayed entering to the tumor at later phase as was observed by sudan stain technique. In conclusion, Re-188 Lipiodol is an effective agent for hepatoma treatment. An optimal activity and injection volume was 2mCi/50μL to the rat hepatoma. Re-188 Lipiodol can retain specifically to the hepatoma for longer time, and excreted by most normal tissues within short time. No accumulation in the bone marrow was found and tumor to normal tissue ratio increased with time, both indicated that Re-188 Lipiodol is an idea agent suitable for treatment of hepatoma as well as for nuclear medicine imaging.

碩士
南台科技大學
生物科技系
97
Background/Aims Hepatoma is the second common cause of cancer death in Taiwan, and its treatment is still far from satisfactory. 188Rhenium (188Re) is a newly developed radioisotope that has short half life, high energy of β-ray and low amount of γ-ray. It can kill liver tumor cells and is convenient for scintigraphy. We inject 188Re into hepatomas in an animal model to evaluate the radioactivities and drug delivery system for the potential clinical applications. Materials and methods The first part of the study is to select N1-S1 cells that can be transplanted to Sprague-Dawley (SD) rats to form a stable hepatoma model. The second part is to evaluate the cancer response to 188Re ECD/lipiodol. After the injection, we check tissue reaction weekly by pathology studies, including hematoxylin and eosin staining, and TUNEL staining. The third part is the pharmacodynamics and pharmacokinetics of 188Re formulae. The fourth part is treatment evaluations on hepatoma transplanted SD-rat models using 188Re ECD/lipiodol, 188Re ECD/lipiodol in a hydrogel delivery system, or normal saline injections. The comparison is based on survival and tissue pathology studies. Results After primary selection, N1-S1 cells become more tumorigenic, as F2>F1>F0; while the tumorigenicity decrease if the cells are passed more than 20 generations, as some of transplanted tumors can disappear spontaneously. The apoptosis of cells were most abundant in 7 days; then, decreased gradually. Pharmacodynamic study shows that the tumor and liver have the highest levels of radioactivities, and 188Re is secreted mostly from urinary system. Survival analysis shows 188Re ECD/Lipiodol group compared with normal saline group have the most significance difference. The thermosensitive hydrogel has improved the delivery of radioactivities, but has some difficulty in injections, which results little improvement of treatment effects overall. Discussion/conclusions Primary selection of cancer cells can improve tumorigenicity, but too many passes of generation can decrease the stability of tumor model. 188Re ECD/lipiodol has good profile for local injection, as it stays well in the tumors. Our animal experiments also validate the potential usefulness of 188Re ECD/lipiodol to treat hepatoma, judging from survival curves and the pathology studies. We expect that 188Re can be used clinically in the near future.

博士
國立中興大學
生命科學系所
101
Background: Advanced or metastatic prostate cancers tend to turn into castration-resistant cancers after hormonal therapy. Most of these cases are characterized by elevated HER2 expression and have poor prognosis. Herceptin (Trastuzumab), a humanized anti-HER2 monoclonal antibody, is widely used for the treatment of patients with HER2-overexpressing breast cancer. However, the application of Herceptin in prostate cancer patients is still controversial. In order to understand whether radioimmunotherapeutic strategy is more effective than immunotherapy by attacking HER2 alone, we labeled the Rhenium-188, a beta emitter, onto Herceptin to evaluate its radioimmunotherapeutic effect on prostate cancer with elevated HER2 expression in vitro and in vivo compared with immunotherapy with Herceptin alone and radiotherapy with Re-188 alone. Methods: DU145, an androgen receptor negative prostate cancer cell line with elevated HER2 expression, was used to evaluate the therapeutic effect of the Herceptin labeled with Rhenium-188 (Re-188), a beta emitter. Its effect is evaluated in vitro on cell growth, extent of apoptosis, protein levels as well as in vivo on bio-distribution, tumor growth, apoptosis and protein levels. Results: The proliferation of DU145 cells was inhibited after treated with the Re-188 Herceptin (Re-H) in dose- and time-dependent manners but not in the control groups treated with PBS (phosphate buffered saline) and Herceptin alone. The proliferate inhibition and apoptosis were induced after Re-H treatment. The in vivo xenograft study revealed tissue-specific bio-distribution of Re-188 Herceptin, which results in significant decrease of tumor growth and correlated changes of apoptosis-related proteins. Moreover, the level of p35 protein, which responds for cancer cell survival and invasion by activating Cdk5, dramatically decreased after Re-188 Herceptin treatment. Conclusion: Our data indicate that Re-188 labeled Herceptin effectively inhibited the growth of DU145 cells compared to the Herceptin- and Re-188-treated cohorts. This implies that targeting Her2 by both radio- and immuno- therapy might be a potential strategy for treating patients with castration-resistant prostate cancer.

碩士
國立清華大學
生醫工程與環境科學系
95
Trastuzumab (Herceptin®), a humanized IgG1 monoclonal antibody directed against the extracellular domain of the HER2 protein, acts as an immunotherapeutic agent for HER2-overexpressing human breast cancers. In this study, 188Re, an emitter with 2.12MeV β- and 0.155MeV γ and t1/2 = 16.9h, was labeled to trastuzumab aiming for radioimmunotherapy of HER2/neu-positive breast cancer. The 188Re(I)-tricarbonyl ion, [188Re(OH2)3(CO)3]+, was employed as a precursor for direct labeling 188Re to the monoclonal antibody. The resultant 188Re(I)-trastuzumab was found to be very stable even challenging with histidine. The tumor and normal tissues localization properties of 188Re(I)-trastuzumab in athymic mice bearing BT-474 human breast cancer xenografts (HER2/neu-overexpressing) and bearing MCF-7 human breast cancer xenografts (HER2/neu-low expressing) were investigated. The in vivo biodistribution study demonstrated that 188Re(I)-trastuzumab was specifically accumulated in BT-474 tumor and the image of 188Re localized BT-474 tumor was clearly visualized within the useful lifetime of the radionuclide. By contrast, the 188Re(I)-trastuzumab uptakes in HER2-low expressing MCF-7 tumor was minimal so that the 188Re image localized at the tumor was not seen. It is revealed from the imaging study that 188Re(I)-trastuzumab may be a potential radioimmunotherapeutic agent for treatment of HER2/neu-overexpressing cancers.