RESUMO
A HPLC-UV-CAD method with a HILIC column for impurity profiling of the 99mTc chelating agent bicisate has been developed and evaluated. Bicisate and its impurities were separated by means of isocratic elution on a zwitterionic stationary phase using a mixture of 7.5mmol/L trifluoroacetic acid and acetonitrile (47.5:52.5 V/V) as the mobile phase. Five different bicisate batches of a manufacturer were tested using the method. In addition LC-MS experiments were conducted in order to identify the impurities. The predominant impurities found were the oxidation product (disulfide), the monoester of ethylene dicysteine and an unknown compound with an m/z of 293 in ESI positive mode. A new degradation product of bicisate, bicisate lactam, was identified during sample solution stability assessment.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cisteína/análogos & derivados , Contaminação de Medicamentos , Compostos de Organotecnécio/análise , Compostos Radiofarmacêuticos/análise , Cromatografia Líquida/métodos , Cisteína/análise , Cisteína/normas , Espectrometria de Massas/métodos , Compostos de Organotecnécio/normas , Compostos Radiofarmacêuticos/normasRESUMO
OBJECTIVES: This study sought to examine current laboratory practices for radiation effective doses for myocardial perfusion imaging (MPI) and laboratory adherence to guideline-directed radiation reduction practices. BACKGROUND: A recent focus on radiation dose reduction for cardiovascular imaging has led to several published guidelines and consensus statements detailing performance metrics for laboratory practices. We sought to examine laboratory adherence to optimized radiation dose protocol recommendations among 5,216 submitted cases from 1,074 MPI laboratories evaluated for Intersocietal Accreditation Commission accreditation. METHODS: Eligible imaging centers included MPI laboratories enrolled in the Intersocietal Accreditation Commission data repository of accreditation applications from 2012 to 2013. Accreditation requires submission of 3 to 5 cases for evaluation of a range of representative cases. Based on standard dosimetry for rest and stress MPI, an effective dose (in millisieverts) was calculated. Model simulations were performed to estimate guideline-directed effective doses. RESULTS: The average effective dose was 14.9 ± 5.8 mSv (range 1.4 to 42.4 mSv). A 1-day technetium Tc 99m protocol was used in 82.9% of cases, whereas a 2-day technetium Tc 99m and dual isotope protocol was used in 7.5% of submitted cases. Only 1.5% of participating imaging centers met current guidelines for an average laboratory radiation exposure ≤9 mSv, whereas 10.1% of patient effective doses were >20.0 mSv. A model simulation replacing the radiation exposure of dual isotope MPI with that of a 1-day technetium Tc 99m protocol reduced the proportion of patients receiving an effective dose >20 mSv to only 2.7% of cases (p < 0.0001). CONCLUSIONS: Mandatory laboratory accreditation for MPI allows for examination of current radiation dosimetry practices. Current guidelines for reduced patient-specific radiation exposure are rarely implemented, with few laboratories meeting recommendations of ≤9 mSv for 50% of patients. Increased educational efforts and the development of performance measures for laboratory accreditation may be required to meet current radiation dose-reduction standards.
Assuntos
Acreditação/normas , Técnicas de Laboratório Clínico/normas , Fidelidade a Diretrizes/normas , Cardiopatias/diagnóstico por imagem , Ensaio de Proficiência Laboratorial/normas , Imagem de Perfusão do Miocárdio/normas , Guias de Prática Clínica como Assunto/normas , Doses de Radiação , Exposição à Radiação/normas , Compostos Radiofarmacêuticos/normas , Simulação por Computador , Circulação Coronária , Bases de Dados Factuais , Cardiopatias/fisiopatologia , Humanos , Imagem de Perfusão do Miocárdio/métodos , Variações Dependentes do Observador , Compostos Organofosforados/normas , Compostos de Organotecnécio/normas , Valor Preditivo dos Testes , Exposição à Radiação/prevenção & controle , Compostos Radiofarmacêuticos/administração & dosagem , Reprodutibilidade dos Testes , Tecnécio Tc 99m Sestamibi/normas , Estados UnidosRESUMO
Technetium-99m ethyl cysteinate dimer (Tc-99m-ECD) is an essential imaging agent used in evaluating the regional cerebral blood flow in patients with cerebrovascular diseases. Determination of active pharmaceutical ingredient, that is, L-Cysteine, N, N'-1,2-ethanediylbis-, diethyl ester, dihydrochloride (ECD) in ECD Kit is a relevant requirement for the pharmaceutical quality control in processes of mass fabrication. We here presented a direct solid sample determination method of ECD in ECD Kit without sample dissolution to avoid the rapid degradation of ECD. An elemental analyzer equipped with a nondispersive infrared detector and a calibration curve of coal standard was used for the quantitation of sulfur in ECD Kit. No significant matrix effect was found. The peak area of coal standard against the amount of sulfur was linear over the range of 0.03-0.10 mg, with a correlation coefficient (r) of 0.9993. Method validation parameters were achieved to demonstrate the potential of this method.
Assuntos
Cisteína/análogos & derivados , Cistina/análogos & derivados , Compostos de Organotecnécio/normas , Compostos Radiofarmacêuticos/normas , Kit de Reagentes para Diagnóstico/normas , Enxofre/análise , Circulação Cerebrovascular , Transtornos Cerebrovasculares/diagnóstico por imagem , Técnicas de Química Analítica , Cisteína/química , Cisteína/normas , Cistina/análise , Estabilidade de Medicamentos , Humanos , Compostos de Organotecnécio/química , Controle de Qualidade , Cintilografia , Compostos Radiofarmacêuticos/químicaRESUMO
OBJECTIVES: Three accumulative tracers, iodine-123-labeled N-isopropyl-p-iodoamphetamine (I-123-IMP), technetium-99m-labeled hexamethylpropyleneamineoxime (Tc-99m-HMPAO), and technetium-99m-labeled ethyl cysteinate dimer (Tc-99m-ECD) are widely used to measure cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). In the present study, normal regional distribution of CBF measured with three different SPECT tracers was entered into a database and compared with regional distribution of CBF measured by positron emission tomography (PET) with H2(15)O. The regional distribution of tissue fractions of gray matter determined by voxel-based morphometry was also compared with SPECT and PET CBF distributions. METHODS: SPECT studies with I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD were performed on 11, 20, and 17 healthy subjects, respectively. PET studies were performed on 11 healthy subjects. Magnetic resonance (MR) imaging studies for voxel-based morphometry were performed on 43 of the 48 subjects who underwent SPECT study. All SPECT, PET, and MR images were transformed into the standard brain format with the SPM2 system. The voxel values of each SPECT and PET image were globally normalized to 50 ml/100 ml/min. Gray matter, white matter, and cerebrospinal fluid images were segmented and extracted from all transformed MR images by applying voxel-based morphometry methods with the SPM2 system. RESULTS: Regional distribution of all three SPECT tracers differed from that of H2150 in the pons, midbrain, thalamus, putamen, parahippocampal gyrus, posterior cingulate gyrus, temporal cortex, and occipital cortex. No significant correlations were observed between the tissue fraction of gray matter and CBF with any tracer. CONCLUSION: Differences in regional distribution of SPECT tracers were considered to be caused mainly by differences in the mechanism of retention of tracers in the brain. Regional distribution of CBF was independent of regional distribution of gray matter fractions, and consequently the blood flow per gray matter volume differed for each brain region.
Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Cisteína/análogos & derivados , Bases de Dados Factuais , Iofetamina , Compostos de Organotecnécio , Tecnécio Tc 99m Exametazima , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Encéfalo/metabolismo , Circulação Cerebrovascular , Cisteína/farmacocinética , Cisteína/normas , Feminino , Humanos , Imageamento Tridimensional/métodos , Imageamento Tridimensional/normas , Iofetamina/farmacocinética , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio/farmacocinética , Compostos de Organotecnécio/normas , Radioisótopos de Oxigênio/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/normas , Compostos Radiofarmacêuticos/farmacocinética , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tecnécio Tc 99m Exametazima/farmacocinética , Tecnécio Tc 99m Exametazima/normas , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/normasRESUMO
The aim of this study was to investigate the mini cartridge versus paper chromatography quality control methods for determining the radiochemical purity (RCP) of (99m)Tc-bicisate. The 4 methods that were compared with the manufacturer's method included Whatman 17 paper/ethyl acetate solvent, instant thin-layer chromatography (ITLC) silica gel paper/saline solvent, reverse-phase C18 mini cartridge/saline solvent, and strong anion exchange mini cartridge/water solvent. At 30 min after reconstitution, (99m)Tc-bicisate was formed at 97%-98% RCP as assayed by the paper and cartridge methods, and the strong anion exchange/water for injection (WFI) system slightly underestimated the percentage at 96%. A significantly lower RCP was obtained for the C18/saline method when a faster flow rate was used. The lipophilic complex moved with ethyl acetate on Whatman 17, was separated from origin impurities on ITLC silica gel/saline, and remained on the column with C18/saline. For strong anion exchange/WFI, components in the radioactive formulation are likely to have influenced the percentage of (99m)Tc-bicisate. The time disadvantage for ITLC silica gel/saline analysis made the method less than ideal. The C18 mini cartridge/saline method was found to be the simplest and fastest; a result was obtained in 2 min with use of a safe solvent of elution.