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Electrochemical studies of the ligand 1-hydroxyl-3-aminopropilydenephosphonic acid (APD) towards bone cancer therapyMagampa, Philemon Podile 22 August 2007 (has links)
The stability constants for the ligand 1-hydroxyl-3-aminopropilydene diphosphonic acid (APD) or Pamidronate with metal ions CdII, PbII and ZnII were established in this work by sampled direct current polarography (DCTAST). Due to precipitation of the metal-ligand complexes in the pH range about 4.0 to 5.0 at typical glass electrode potentiometric conditions, these systems could not be studied by glass electrode potentiometry (GEP). The concept of Virtual Potentiometry (VP) was used in the modelling of the metal-ligand system and refinement of stability constants to evaluate further the metal-ligand models derived from DCTAST. Virtual potentiometry uses virtual potentials to refine polarographic data by employing dedicated potentiometric software, ESTA. The structure of the metal complexes determined in this work is also proposed and compared to the reported crystal structures of the metal complexes of the ligand APD. The Linear Free Energy Relationship, LFER (log KML′ vs. log KM(OH) ) for the ligand APD is derived here for the first time using the log KML′ values from literature as well as the values for CdII, PbII and ZnII determined in this work. The log KML′ values of 153SmIII–APD and 166HoIII–APD, which cannot be determined by these two techniques (GEP and DCTAST), were predicted in this work using the LFER methodology. / Dissertation (MSc (Chemistry))--University of Pretoria, 2006. / Chemistry / MSc / Unrestricted
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Synthesis and radiochemical stability evaluation of radiopharmaceutical compounds containing radioiodinated prosthetic groupsRossouw, Daniel Du Toit 12 1900 (has links)
Thesis (PhD)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: A study was undertaken to investigate the radiochemical stability of the βiodoethoxyl moiety,
a relatively novel prosthetic group employed in radiopharmaceutical chemistry, in which an
oxygen atom in a β-position relative to the radioiodine atom has a stabilising effect on the
aliphatic carbon-iodine bond. The investigation was started as a pilot study by synthesising
various model compounds containing a β-radioiodoethoxyl moiety, as well as two reference
compounds lacking such a moiety. The purpose was to determine the influence of various
groups in the vicinity of the β-oxygen atom on the stability of the abovementioned moiety.
Radiochemical stability tests were carried out in vitro at 37°C in human blood serum. The
results confirmed the superior stability of such a moiety compared to that of the reference
compounds and also showed that the branching of such an aliphatic unit resulted in a
considerable improvement in its stability, especially over a longer period.
The investigation was extended to the synthesis of other compounds containing a few selected
β-iodoethoxyl moieties that showed improved stability in the pilot study work. Reference
compounds containing the classical iodovinyl unit, as well as those lacking a stabilising β-
oxygen atom, were also prepared. The carrier molecules used in this part of the work was a
benzamide containing a phenolic oxygen atom which acted as the β-oxygen atom, as well as
two heterocyclic amines, benzotriazole and 2-methyl-5-nitroimidazole, in which the β-
iodoethoxyl moiety was linked to a secondary nitrogen atom. Various suitable alkylating agents
were prepared, chemically linked to the carrier molecules, the resulting intermediate
compounds converted into tosylate or triflate iodination precursors and labelled with
radioiodine by means of iodide-for-tosylate/triflate exchange. In vitro stability tests of these
compounds showed similar trends to those obtained with the model compounds. Moreover, the
stability of the stabilised β-iodoethoxyl moiety compared favourably with that of the iodovinyl
unit, especially when incorporated into a heterocyclic amine. The results of this study have shown that some of the radioiodinated compounds synthesized in this work, especially the
nitroimidazole derivatives, have the potential to be considered as novel radiopharmaceuticals. / AFRIKAANSE OPSOMMING: 'n Studie is onderneem om die radiochemiese stabiliteit van die β-jodium-etoksi-eenheid te
ondersoek. Dié eenheid is 'n relatief nuwe prostetiese groep wat in radiofarmaseutiese chemie
gebruik word. Die suurstofatoom wat in 'n β-posisie relatief tot die radiojodiumatoom
voorkom, oefen 'n stabiliserende invloed op die alifatiese koolstof-jodiumbinding uit. Die
ondersoek het met 'n loodsstudie begin deur verskillende modelverbindings te sintetiseer wat 'n
β-radiojodium-etoksi-eenheid bevat, asook twee verwysingsverbindings waarin so 'n eenheid
ontbreek. Die doel hiermee was om die invloed van verskillende groepe, wat in die omgewing
van die β-suurstofatoom voorkom, op die stabiliteit van die eenheid te bepaal. Radiochemiese
stabiliteitstoetse is uitgevoer deur middel van inkubering in menslike bloedserum by 37°C. Die
resultate het die groter stabiliteit van so 'n eenheid in vergelyking met dié van die
verwysingsverbindings aangetoon, en het ook uitgewys dat vertakking van so 'n alifatiese
eenheid 'n aansienlike verbetering in die stabiliteit tot gevolg gehad het, veraloor 'n langer
periode.
Die ondersoek is vervolgens uitgebrei deur verdere verbindings te sintetiseer wat beskik oor
bepaalde uitgesoekte β-jodium-etoksi-eenhede, wat verbeterde stabiliteit in die loodsstudie
getoon het. Verwysingsverbindings wat die klassieke jodiumvinieleenheid bevat het, sowel as
dié waarin 'n stabiliserende β-suurstofatoom ontbreek het, is ook berei. Die draermolekules
wat in hierdie deel van die studie gebruik is, was 'n bensamied met 'n fenoliese suurstofatoom
wat as die β-suurstofatoom gedien het, sowel as twee heterosikliese amiene, bensotriasool en 2-
metiel-5-nitroimidasool, waarin die β-jodium-etoksi-eenheid aan 'n sekondêre stikstofatoom
geheg is. Verskillende geskikte alkileermiddels is berei, aan die draermolekules geheg, die
tussenprodukte omskep in tosilate of triflate en met radiojodium gemerk deur middel van
jodium-vir-tosilaatltriflaat-uitruiling. Stabiliteitstoetse van hierdie verbindings in bloedserum
het soortgelyke tendense as dié van die aanvanklike modelverbindings getoon. Daarbenewens
het die stabiliteit van die gestabiliseerde β-jodium-etoksi-eenheid gunstig vergelyk met dié van die jodiumviniel-eenheid, veral wanneer dit deel gevorm het van 'n heterosikliese amien. Die
resultate van die studie het getoon dat sommige van die radiogejodeerde verbindings wat berei
is, veral die nitroimidasoolderivate, die potensiaal het om as nuwe radiofarmaseutiese
verbindings gebruik te kan word.
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Determinação de endotoxina bacteriana (pirogênio) em radiofármacos pelo método de formação de gel. Validação / Determination of bacterial endotoxin (pyrogen) in radiopharmaceuticals by the gel clot method. Validation.Fukumori, Neuza Taeko Okasaki 28 February 2008 (has links)
Antes do Ensaio do Lisado de Amebócitos do Limulus (LAL), a única forma de se avaliar a pirogenicidade em drogas parenterais e dispositivos médicos era o ensaio de pirogênio em coelhos da Farmacopéia Americana (USP). Especialmente para radiofármacos, o ensaio LAL é a escolha para a determinação de endotoxina bacteriana (pirogênio). O objetivo deste trabalho foi validar o método de formação de gel para alguns radiofármacos sem uma interferência mensurável. O guia do método LAL do Food and Drug Administration (FDA) define interferência como uma condição que causa uma diferença significativa entre os pontos finais de gelificação das séries de controle positivo da água e controle positivo do produto utilizando-se um endotoxina padrão. Os experimentos foram realizados de acordo com o teste de endotoxinas bacterianas da USP na m-iodobenzilguanidina-131I, nos radioisótopos Gálio-67 e Tálio-201, nos reagentes liofilizados DTPA, Fitato, GHA, SAH e Sn Coloidal. A Máxima Diluição Válida (MDV) foi calculada para cada produto com base na sua dose clínica e diluições seriadas abaixo da MDV foram avaliadas em duplicata para a detecção de interferências. A sensibilidade declarada do reagente de LAL foi de 0,125 UE mL-1 (Unidades de Endotoxina por mililitro). Para a validação, uma série de diluições foi feita utilizando-se padrão de endotoxina (PE) nas concentrações de 0,5 a 0,03 UE mL-1 para a confirmação da sensibilidade do reagente de LAL, em quadruplicata. A mesma série de diluições foi feita com o PE e o produto diluído 100 vezes em três lotes consecutivos de cada radiofármaco. Os produtos m-iodobenzilguanidina-131I, Gálio-67, Tálio-201, DTPA, SAH e Sn Coloidal foram compatíveis com o método no fator de diluição 1:100. Fitato e GHA apresentaram interferência no ensaio de formação de gel. Outras técnicas para determinar endotoxinas como o ensaio cromogênico (desenvolvimento de cor) e o turbidimétrico (desenvolvimento de turbidez) foram avaliadas para obter informações qualitativas e quantitativas sobre as concentrações de endotoxinas nas amostras. / Before the Limulus amebocyte lysate (LAL) test, the only available means of pirogenicity testing for parenteral drugs and medical devices was the United States Pharmacopoeia (USP) rabbit pyrogen test. Especially for radiopharmaceuticals, the LAL assay is the elective way to determine bacterial endotoxin. The aim of this work was to validate the gel clot method for some radiopharmaceuticals without measurable interference. The FDAs LALTest guideline defines interference as a condition that causes a significant difference between the endpoints of a positive water control and positive product control series using a standard endotoxin. Experiments were performed in accordance to the USP bacterial endotoxins test in the 131I- m-iodobenzylguanidine; the radioisotopes Gallium-67 and Thallium-201; the liophylized reagents DTPA, Phytate, GHA, HSA and Colloidal Tin. The Maximum Valid Dilution (MVD) was calculated for each product based upon the clinical dose of the material and a twofold serial dilution below the MVD was performed in duplicate to detect interferences. The labeled sensitivity of the used LAL reagent was 0.125 EU mL-1 (Endotoxin Units per milliliter). For validation, a dilution series was performed, a twofold dilution of control standard endotoxin (CSE) from 0.5 to 0.03 EU mL-1, to confirm the labeled sensitivity of the LAL reagent being tested in sterile and non pyrogenic water, in quadruplicate. The same dilution series was performed with the CSE and the product in the 1:100 dilution factor, in three consecutive batches of each radiopharmaceutical. The products 131I-m-iodobenzylguanidine, Gallium-67, Thallium-201, DTPA, HSA and Colloidal Tin were found compatible with the LAL test at a 1:100 dilution factor. Phytate and GHA showed some interference in the gel clot test. Other techniques to determine endotoxins as the chromogenic (color development) and the turbidimetric test (turbidity development), were also assessed to get valuable quantitative and qualitative information about the endotoxin concentration in samples.
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Complexos de interesse medicinal em terapia ou diagnóstico, envolvendo os elementos Au, Pd, Pt, Re e Tc, com tiossemicarbazonas S,N,S-tridentadas / Complexes of medicinal interest in terapy and diagnostics, involving the elements Au, Pd, Pt, Re and Tc with S,N,S-tridentate thiosemicarbazonesMaia, Pedro Ivo da Silva 01 December 2011 (has links)
Esta tese apresenta a síntese de uma nova classe de tiossemicarbazonas/tiossemicarbazidas (H2L1) potencialmente S,N,S-doadoras, obtida através de reações entre cloreto de N-[N\',N\'-dialquilamino(tiocarbonil)]benzimidoílas e 4,4-dialquiltiossemicarbazidas, as quais apresentaram um efeito citotóxico bastante promissor contra células de câncer de mama humano da linhagem MCF-7. Estas tiossemicarbazonas foram utilizadas na preparação de novos complexos de metais de transição, incluindo os elementos Au, Pd, Pt, Re e Tc, os quais foram caracterizados com base em espectroscopias no IV, absorção no UV-vis, massa, 1H- e 31P-RMN, análise elementar, difração de raios X em monocristal e cálculos teóricos. <br />Os resultados obtidos para os complexos de ouro apresentaram destaque. Eles foram sintetizados através de reações do Na[AuCl4]•2H2O com os ligantes tiossemicarbazonas H2L1, com a formação de complexos verdes estáveis ao ar [AuCl(L1)]. Pequenas quantidades de complexos de ouro(I) de composição [AuCl(L3)] se formaram como produtos laterais, onde L3 é o ligante 5-dietilamino-3-fenil-1-tiocarbamoil-1,2,4-triazol. Um caminho da reação de redução foi proposto com base nos dados de espectroscopia de massa e análise da estrutura cristalina. Reações de substituição nos complexos [AuCl(L1)] também foram investigadas. Cálculos por DFT dos complexos [AuCl(L1)] e dos produtos das reações de troca mostraram que o quarto ligante na esfera de coordenação influencia fortemente a densidade eletrônica no centro metálico. A deficiência eletrônica do centro metálico parece estar relacionada com a inibição do crescimento celular em células de câncer de mama destes complexos de ouro(III). Os complexos de ouro descritos neste trabalho representam os primeiros exemplos de complexos de ouro(III) com tiossemicarbazonas totalmente caracterizados. <br />Complexos de platina(II) e paládio(II) contendo os ligantes H2L1 também foram preparados de modo a se comparar a atividade biológica com os complexos de ouro(III) análogos. Os ligantes H2L1 reagem, com desprotonação única, com [PdCl2(MeCN)2] ou [PtCl2(COD)] para formar complexos quelatos estáveis ao ar com fórmula geral [MCl(HL1)] (M = Pd ou Pt). A presença de um hidrogênio ionizável na estrutura dos ligantes monodesprotonados dos complexos [MCl(HL1)] permitiu a investigação de reações com adição de base, as quais forneceram complexos oligoméricos. Além disso, mostrou-se que o ligante cloro em [PdCl(HL1)] pode ser substituído por um ligante tiofenolato (tfol-), sem desprotonação adicional do ligante HL1-, formando complexos do tipo [Pd(HL1)(tfol)]. <br />Complexos de oxorrênio(V) de composição geral [ReOCl(L1)], os quais são formados através de reações dos ligantes H2L1 com (NBu4)[ReOCl4], também foram sintetizados e caracterizados. O ligante cloro dos complexos [ReOCl(L1)] também foi trocado por outros ligantes monodentados. Entretanto, variações na relação estequiométrica bem como nas condições reacionais podem resultar em diferentes produtos, podendo ocorrer a coordenação de duas unidades do ligante monodentado substituinte, sendo a segunda na posição trans ao grupo oxo. Além disso, complexos de oxorrênio(V) do tipo \"3+2\" [ReO(Ph2btu)(L1)], onde Ph2btu- = N,N-fenil-N\'-benzoiltiouréia, também foram obtidos. Os efeitos antiproliferativos do sistema [ReO(X)(L)], onde X é um ligante monodentado ou bidentado, sobre células de câncer de mama foram investigados extensivamente em experimentos in vitro, os quais mostraram que a labilidade do ligante cloro apresenta um papel chave na atividade citotóxica. <br />Finalmente, complexos de rênio(V) contendo o fragmento Re(NPh)3+ e os ligantes H2L1 foram sintetizados e totalmente caracterizados, incluindo análises por difração de raios X. Do mesmo modo, complexos com Tc(NPh)3+ (isótopo 99Tc) e os ligantes H2L1 também foram preparados e caracterizados por métodos espectroscópicos. Uma comparação dos complexos de rênio com os de tecnécio mostrou que estes apresentam analogia estrutural. A forte habilidade quelante dos ligantes H2L1 bem como as suas propriedades anticâncer, indicam seus derivados de tecnécio para futuras aplicações como radiofármacos. / This thesis presents the synthesis of a new class of thiosemicarbazones/thiosemicarbazides (H2L1) potentially S,N,S-donors, obtained by reactions of N-[N\',N\'-diethylamino(thiocarbonyl)]benzimidoyl chloride and 4,4-dialkylthiosemicarbazides, which were found to present a remarkable antiproliferative effect against human MCF-7 breast cancer cells. These thiosemicarbazones were used to prepare new transition metal complexes, including the elements Au, Pd, Pt, Re and Tc; which have been characterized based on IR, UV-vis absorption, mass, 1H- and 31P-NMR spectroscopies, elemental analysis, X-ray diffractometry from single crystals and theoretical calculations. <br />The results obtained with the gold complexes were highlighted. They were synthesized by reactions of Na[AuCl4]•2H2O with the thiosemicarbazone ligands H2L1, under formation of air-stable green [AuCl(L1)] complexes. Small amounts of gold(I) complexes of the composition [AuCl(L3)] were formed as side-products, where L3 is the 5-diethylamino-3-phenyl-1-thiocarbamoyl-1,2,4-triazole ligand. A pathway of the reduction reaction was proposed on the basis of mass spectroscopy and crystal structure analysis. Substitution reactions on the complexes were also investigated. DFT calculations carried out on [AuCl(L1)] and the products of the exchange reactions showed that the fourth ligand in the coordination sphere strongly influences the electron density on the metal center. The metal center\'s electron deficiency seems to be related with the cell growth inhibition against breast cancer cells of these gold(III) complexes. The gold complexes described in this work represent the first examples of fully characterized neutral Au(III) thiosemicarbazone complexes. <br />Platinum(II) and palladium(II) complexes containing the H2L1 ligands have also been prepared in order to compare their biological activity with those of the gold(III) analogs. H2L1 ligands react under single deprotonation with [PdCl2(MeCN)2] or [PtCl2(COD)] to form air-stable chelate complexes with general formula [M(HL1)Cl] (M = Pd or Pt). The presence of an ionizable hydrogen atom in the structure of the monodeprotonated ligands of the [M(HL1)Cl] complexes allowed the investigation of reactions with addition of base, which afforded oligomeric complexes. Furthermore, it has been shown that the chlorido ligand in [PdCl(HL1)] may be replaced by a thiophenolato ligand (tfol-) without additional deprotonation of the HL1- ligand, forming [Pd(HL1)(tfol)] type complexes. <br />Oxorhenium(V) complexes of the general composition [ReOCl(L1)], which are formed by reactions of H2L1 with (NBu4)[ReOCl4], have also been synthesized and characterized. The chorido ligand the [ReOCl(L1)] complexes was also replaced by other monodentade ligands. However, changes in the stoichiometry as well as in the reaction conditions may result in different products, so that two units of the monodentate ligand may coordinate, with the second one trans positioned to the oxo group. In addition, oxorhenium(V) complexes of the type \"3+2\" [ReO(L1)(Ph2btu)], where Ph2btu- = N,N-phenyl-N\'-benzoylthiourea, have also been obtained. The antiproliferative effects of the [ReO(X)(L)] system, where X is a monodentade or a bidentate ligand, on breast cancer cells was extensively investigated in in vitro experiments, which showed that the lability of the chlorido ligand plays a key role in the cytotoxic activity. <br />Finally, Re(V) complexes containing the phenylimido core Re(NPh)3+ and H2L1 ligands have been synthesized and fully characterized, including X-ray diffraction analysis. As well, complexes with Tc(NPh)3+ (99Tc isotope) were also prepared and characterized by spectroscopic methods. A comparison of the rhenium and the technetium complexes showed that they present structural analogy. The strong chelate ability of the H2L1 as well as the anticancer properties, indicate their technetium derivatives for future applications as radiopharmaceutical.
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Determinação de endotoxina bacteriana (pirogênio) em radiofármacos pelo método de formação de gel. Validação / Determination of bacterial endotoxin (pyrogen) in radiopharmaceuticals by the gel clot method. Validation.Neuza Taeko Okasaki Fukumori 28 February 2008 (has links)
Antes do Ensaio do Lisado de Amebócitos do Limulus (LAL), a única forma de se avaliar a pirogenicidade em drogas parenterais e dispositivos médicos era o ensaio de pirogênio em coelhos da Farmacopéia Americana (USP). Especialmente para radiofármacos, o ensaio LAL é a escolha para a determinação de endotoxina bacteriana (pirogênio). O objetivo deste trabalho foi validar o método de formação de gel para alguns radiofármacos sem uma interferência mensurável. O guia do método LAL do Food and Drug Administration (FDA) define interferência como uma condição que causa uma diferença significativa entre os pontos finais de gelificação das séries de controle positivo da água e controle positivo do produto utilizando-se um endotoxina padrão. Os experimentos foram realizados de acordo com o teste de endotoxinas bacterianas da USP na m-iodobenzilguanidina-131I, nos radioisótopos Gálio-67 e Tálio-201, nos reagentes liofilizados DTPA, Fitato, GHA, SAH e Sn Coloidal. A Máxima Diluição Válida (MDV) foi calculada para cada produto com base na sua dose clínica e diluições seriadas abaixo da MDV foram avaliadas em duplicata para a detecção de interferências. A sensibilidade declarada do reagente de LAL foi de 0,125 UE mL-1 (Unidades de Endotoxina por mililitro). Para a validação, uma série de diluições foi feita utilizando-se padrão de endotoxina (PE) nas concentrações de 0,5 a 0,03 UE mL-1 para a confirmação da sensibilidade do reagente de LAL, em quadruplicata. A mesma série de diluições foi feita com o PE e o produto diluído 100 vezes em três lotes consecutivos de cada radiofármaco. Os produtos m-iodobenzilguanidina-131I, Gálio-67, Tálio-201, DTPA, SAH e Sn Coloidal foram compatíveis com o método no fator de diluição 1:100. Fitato e GHA apresentaram interferência no ensaio de formação de gel. Outras técnicas para determinar endotoxinas como o ensaio cromogênico (desenvolvimento de cor) e o turbidimétrico (desenvolvimento de turbidez) foram avaliadas para obter informações qualitativas e quantitativas sobre as concentrações de endotoxinas nas amostras. / Before the Limulus amebocyte lysate (LAL) test, the only available means of pirogenicity testing for parenteral drugs and medical devices was the United States Pharmacopoeia (USP) rabbit pyrogen test. Especially for radiopharmaceuticals, the LAL assay is the elective way to determine bacterial endotoxin. The aim of this work was to validate the gel clot method for some radiopharmaceuticals without measurable interference. The FDAs LALTest guideline defines interference as a condition that causes a significant difference between the endpoints of a positive water control and positive product control series using a standard endotoxin. Experiments were performed in accordance to the USP bacterial endotoxins test in the 131I- m-iodobenzylguanidine; the radioisotopes Gallium-67 and Thallium-201; the liophylized reagents DTPA, Phytate, GHA, HSA and Colloidal Tin. The Maximum Valid Dilution (MVD) was calculated for each product based upon the clinical dose of the material and a twofold serial dilution below the MVD was performed in duplicate to detect interferences. The labeled sensitivity of the used LAL reagent was 0.125 EU mL-1 (Endotoxin Units per milliliter). For validation, a dilution series was performed, a twofold dilution of control standard endotoxin (CSE) from 0.5 to 0.03 EU mL-1, to confirm the labeled sensitivity of the LAL reagent being tested in sterile and non pyrogenic water, in quadruplicate. The same dilution series was performed with the CSE and the product in the 1:100 dilution factor, in three consecutive batches of each radiopharmaceutical. The products 131I-m-iodobenzylguanidine, Gallium-67, Thallium-201, DTPA, HSA and Colloidal Tin were found compatible with the LAL test at a 1:100 dilution factor. Phytate and GHA showed some interference in the gel clot test. Other techniques to determine endotoxins as the chromogenic (color development) and the turbidimetric test (turbidity development), were also assessed to get valuable quantitative and qualitative information about the endotoxin concentration in samples.
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A web-based medical radionuclide databaseJue, Tracy M. 24 May 1999 (has links)
Currently the Food and Drug Administration publishes radiopharmaceutical
information for physicians to choose appropriate medical diagnosis and therapy for their
patients. The primary functions of these radiopharmaceuticals are diagnosis and
delivering doses to a patient with appropriate energy, biological half life, chemical
behavior, and radiological half life. These radiopharmaceuticals preferentially react with
certain type of cells. Diagnosis or therapy must be accurately prepared for and planned
by medical professionals. The fast access to the internet has become a key tool for
medical professionals to obtain this type of information. A web page has been developed
that links nuclear and biological data to radiopharmaceutical information. Queries can be
performed on this database to sort the radiopharmaceuticals by radiological half life,
gamma energy, biological half life, medical application, chemical information or other
parameters. This capability allows medical professionals and scientists to select
radiopharmaceuticals by their characteristics. There are approximately 100 medical
isotopes in the database. / Graduation date: 2000
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Synthesis and characterization of ¹⁰⁵Rh-labeled thiamacrocycles for use to formulate peptide receptor agents /Li, Ning, January 1996 (has links)
Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves 126-141). Also available on the Internet.
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Design and development of novel phosphine - based chelating systems for chemical and biomedical motifs /Gali, Hariprasad, January 1999 (has links)
Thesis (Ph. D.)--University of Missouri-Columbia, 1999. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.
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Design and development of novel phosphine - based chelating systems for chemical and biomedical motifsGali, Hariprasad, January 1999 (has links)
Thesis (Ph. D.)--University of Missouri-Columbia, 1999. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.
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Synthesis of water soluble organophosphines and phospine-peptide conjugates : investigations on the biomedical utility of their transition metal complexes /Pillarsetty, Nagavarakishore, January 2003 (has links)
Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 186-205). Also available on the Internet.
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