RESUMO
PURPOSE: To evaluate the reliability of pelvimetric measurements performed using stereoradiographic imaging (SRI), and to assess maternal and fetal radiation doses compared to low-dose computer tomography (CT) pelvimetry. MATERIALS AND METHODS: Thirty-five pregnant women (mean age, 29.6±5.5 [SD] years; range: 20-41 years) were prospectively included. All women underwent simultaneous frontal and lateral low-dose SRI and low-dose CT examination of the pelvis. Pelvimetry measurements were obtained from both examinations and radiation doses obtained with the two techniques were compared. RESULTS: SRI-CT correlation (Pearson coefficient correlation [r]; mean bias [mb]) was strong for transverse inlet diameter (r=0.92; mb=-0.09cm), anteroposterior diameter of the pelvic inlet (r=0.92; mb = 0.47cm), maximal transverse diameter (r=0.9; mb=0.21cm), sacrum length (r=0.9; mb=0.09cm). Correlation was good. Correlation was good for the sacrum depth (r=0.75; mb=0.06cm) and Magnin's index (r=0.7; mb=0.5cm). Correlation was moderate for anteroposterior diameter of pelvic outlet (r=0.6; mb=0.52cm). The fetal dose was 13.1 times lower using SRI (87±26µGy) than CT (1140±220µGy, P<0.0001). The effective maternal dose was 3.1 times lower using SRI (97±21µSv) than CT (310±60µSv; P<0.0001). CONCLUSION: Pelvic inlet measurements using SRI are reliable. Compared to CT pelvimetry, SRI leads to a significant decrease in fetal and maternal radiation doses. These findings should prompt physicians to use SRI as the first-line approach for pelvimetry.
Assuntos
Pelvimetria/métodos , Pelve/diagnóstico por imagem , Análise Radioestereométrica/métodos , Tomografia Computadorizada por Raios X , Adulto , Feminino , Humanos , Gravidez , Estudos Prospectivos , Doses de Radiação , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Positron emission tomography (PET) systems dedicated to animal imaging are now widely used for biological studies. The scanner performance strongly depends on the design and the characteristics of the system. Many parameters must be optimized like the dimensions and type of crystals, geometry and field-of-view (FOV), sampling, electronics, lightguide, shielding, etc. Monte Carlo modelling is a powerful tool to study the effect of each of these parameters on the basis of realistic simulated data. Performance assessment in terms of spatial resolution, count rates, scatter fraction and sensitivity is an important prerequisite before the model can be used instead of real data for a reliable description of the system response function or for optimization of reconstruction algorithms. The aim of this study is to model the performance of the Philips Mosaic animal PET system using a comprehensive PET simulation code in order to understand and describe the origin of important factors that influence image quality. We use GATE, a Monte Carlo simulation toolkit for a realistic description of the ring PET model, the detectors, shielding, cap, electronic processing and dead times. We incorporate new features to adjust signal processing to the Anger logic underlying the Mosaic system. Special attention was paid to dead time and energy spectra descriptions. Sorting of simulated events in a list mode format similar to the system outputs was developed to compare experimental and simulated sensitivity and scatter fractions for different energy thresholds using various models of phantoms describing rat and mouse geometries. Count rates were compared for both cylindrical homogeneous phantoms. Simulated spatial resolution was fitted to experimental data for (18)F point sources at different locations within the FOV with an analytical blurring function for electronic processing effects. Simulated and measured sensitivities differed by less than 3%, while scatter fractions agreed within 9%. For a 410-665 keV energy window, the measured sensitivity for a centred point source was 1.53% and mouse and rat scatter fractions were respectively 12.0% and 18.3%. The scattered photons produced outside the rat and mouse phantoms contributed to 24% and 36% of total simulated scattered coincidences. Simulated and measured single and prompt count rates agreed well for activities up to the electronic saturation at 110 MBq for the mouse and rat phantoms. Volumetric spatial resolution was 17.6 microL at the centre of the FOV with differences less than 6% between experimental and simulated spatial resolution values. The comprehensive evaluation of the Monte Carlo modelling of the Mosaic system demonstrates that the GATE package is adequately versatile and appropriate to accurately describe the response of an Anger logic based animal PET system.
Assuntos
Tomografia por Emissão de Pósitrons/instrumentação , Animais , Fenômenos Biofísicos , Biofísica , Tamanho Corporal , Camundongos , Modelos Estatísticos , Método de Monte Carlo , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Ratos , Espalhamento de Radiação , Sensibilidade e Especificidade , Software , Design de SoftwareRESUMO
PURPOSE: To estimate fetal absorbed doses for pregnant women pelvimetry, a comparative study between EOS imaging system and low-dose spiral CT-scanner was carried out. For this purpose three different studies were investigated: in vivo, in vitro and Monte Carlo calculations. METHODS: In vivo dosimetry was performed, using OSL NanoDot dosimeters, to determine the dose to the skin of twenty pregnant women. In vitro studies were established by using a cubic phantom of water, in order to estimate the out of field doses. In the latter study, OSLDs were placed at depths corresponding to the lowest, average and highest position of the uterus. Monte Carlo calculations of effective doses to high radio-sensitive organs were established, using PCXMC and CTExpo software suites for EOS imaging system and CT-scanner, respectively. RESULTS: The EOS imaging system reduces radiation exposure 4 to 8 times compared to the CT-scanner. The entrance skin doses were 74% (p-values <0.01) higher with the CT-scanner than with the EOS system. In the out of field region, the measured doses of the EOS system were reduced by 80% (p-values <0.02). Monte Carlo calculations confirmed that effective doses to organs are less accentuated for EOS than for CT pelvimetry. CONCLUSIONS: The EOS system is less irradiating than the CT exam. The out-of-field dose which is significant, is lower in the EOS than in the CT-scanner and could be reduced even further by optimizing the time used for image acquisition.
Assuntos
Pelvimetria/instrumentação , Doses de Radiação , Tomografia Computadorizada por Raios X/instrumentação , Feminino , Feto/efeitos da radiação , Humanos , Método de Monte Carlo , Órgãos em Risco/efeitos da radiação , Gravidez , Tomografia Computadorizada por Raios X/efeitos adversosRESUMO
UNLABELLED: To report a retrospective study concerning the impact of fused 18F-fluorodeoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on three-dimensional conformal radiation therapy (3D-CRT) planning for patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred and one patients consecutively treated for stages I-III NSCLC were studied. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same radiation treatment position. Images were coregistered using five fiducial markers. Target volume delineation was initially performed on the CT images and the corresponding FDG-PET data were subsequently used as an overlay to the CT data to define target volume. RESULTS: FDG-PET identified previously undetected distant metastatic disease in 8 patients making them ineligible for curative CRT (one patient presented some positive uptakes corresponding to concomitant pulmonary tuberculosis). Another patient was ineligible for curative treatment because fused CT/PET images demonstrated excessively extensive intrathoracic disease. The gross tumor volume (GTV) was decreased by CT/PET image fusion in 21 patients (23%) and was increased in 24 patients (26%). The GTV reduction was > or = 25% in 7 patients because CT/PET image fusion reduced pulmonary GTV in 6 patients (3 patients with atelectasis) and mediastinal nodal GTV in 1 patient. The GTV increase was > or = 25% in 14 patients due to an increase of the pulmonary GTV in 11 patients (4 patients with atelectasis) and detection of occult mediastinal lymph node involvement in 3 patients. Among 81 patients receiving a total dose > or = 60 Gy at ICRU point, after CT/PET image fusion, the percentage of total lung volume receiving more than 20 Gy (VL20) increased in 15 cases and decreased in 22 cases. The percentage of total heart volume receiving more than 36 Gy increased in 8 patients and decreased in 14 patients. The spinal cord volume receiving at least 45 Gy (2 patients) decreased. After multivariate analysis, one single independent factor made significant effect of FDG/PET on the modification of the size of the GTV: tumor with atelectasis (P = 0.0001). Conclusion. - Our study confirms that integrated hybrid PET/CT in the treatment position and coregistered images have an impact on treatment planning and management of patients with NSCLC. FDG images using dedicated PET scanners with modern image fusion techniques and respiration-gated acquisition protocols could improve CT/PET image coregistration. However, prospective studies with histological correlation are necessary and the impact on treatment outcome remains to be demonstrated.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Tomografia por Emissão de Pósitrons , Radioterapia Conformacional/métodos , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Atelectasia Pulmonar/patologia , Compostos Radiofarmacêuticos , Dosagem Radioterapêutica , Estudos RetrospectivosRESUMO
UNLABELLED: Somatostatin receptor scintigraphy (SRS) has been used for the detection of gastroenteropancreatic (GEP) tumors. This study evaluates the clinical impact of SRS in GEP tumor detection and its therapeutic implications on patient management. METHODS: We prospectively studied 160 patients with biologically and/or histologically proven GEP tumors. Before SRS, patients were classified into three groups: gastrointestinal (Group 1; n = 90) patients without known metastases; (Group 2; n = 59) patients with metastases limited to the liver; (Group 3; n = 11) patients with known extrahepatic metastases. The scintigraphic data were compared to the radiological findings. RESULTS: In Group 1, without known metastases, conventional imaging detected 53 primary sites in 44 patients: SRS was positive in 68% of these sites and discovered 4 additional primary tumors in 3 patients and 16 metastases in 14 patients. Conventional imaging was negative in 46 patients: SRS discovered 47 new sites in 36 patients. In Group 2, SRS confirmed liver metastases in 95% of patients and discovered 45 new sites in 36 of these patients. In Group 3, SRS disclosed 11 new sites in 7 patients. These results modified patient classification in 38 cases (24%). Surgical therapeutic strategy was changed in 40 patients (25%). CONCLUSION: Somatostatin receptor scintigraphy improves tumor detection, has major clinical significance and should be performed systematically for staging and therapeutic decision making in patients with GEP tumors.
Assuntos
Tumor Carcinoide/diagnóstico por imagem , Neoplasias Gastrointestinais/diagnóstico por imagem , Radioisótopos de Índio , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Receptores de Somatostatina/análise , Somatostatina/análogos & derivados , Síndrome de Zollinger-Ellison/diagnóstico por imagem , Tumor Carcinoide/secundário , Estudos de Casos e Controles , Diagnóstico por Imagem , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/secundário , Estudos Prospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
A patient with previous left caudal pancreatectomy and splenectomy presented with Zollinger-Ellison syndrome. Abdominal CT and endoscopic ultrasonography revealed a mass in the splenic area. Somatostatin receptor scintigraphy showed a nodular increase of the uptake corresponding to the lesion detected with conventional imaging. A second laparotomy was performed and the mass was resected. Histological analysis showed that the nodular lesion was an accessory spleen. Since physiologic uptake of 111In-pentetreotide is seen in the spleen, an accessory spleen mimicking a tumor, specially after previous splenectomy, may result in false-positive somatostatin receptor scintigraphy.
Assuntos
Radioisótopos de Índio , Receptores de Somatostatina/análise , Somatostatina/análogos & derivados , Baço/anormalidades , Síndrome de Zollinger-Ellison/diagnóstico por imagem , Reações Falso-Positivas , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Baço/diagnóstico por imagemRESUMO
Determination of the biodistribution of radiopharmaceuticals is an important issue for the evaluation of their performance in diagnosis and therapy. In this study, we evaluated a digital radioimager (RI) based on a multiwire proportional chamber for quantitative autoradiography (AR). The RI allows direct detection of electronic emissions of gamma emitters. Its qualitative and quantitative performances were tested on 99mTc and (111)In labelled sections and compared with conventional film AR. Linearity of count rate versus activity was verified over a 104 range of activity. As compared with film AR, a substantial improvement of the detection limit was obtained even for acquisition periods up to 20 times less than film exposure times. We provided the basis for quantitative analysis with tissue equivalent paste standards: the 99mTc and (111)In RI counting efficiencies were respectively 1.19% and 2.35%. We illustrated the respective values of RI and film AR in two rat studies: 99mTc-DMSA in kidney and dual-isotope 99mTc-MIBI and (111)In-antimyosin in heart. Calculated activity concentrations on sections of rat organs confirmed good correlation to gamma counting (deviation less than 12%). We suggest RI as a convenient technique for fast localization of single or dual-isotope tracers and determination of activity distribution.
Assuntos
Autorradiografia/instrumentação , Rim/química , Miocárdio/química , Medicina Nuclear/instrumentação , Compostos Radiofarmacêuticos/análise , Animais , Interpretação Estatística de Dados , Radioisótopos de Índio/análise , Masculino , Ratos , Ratos Wistar , Ácido Dimercaptossuccínico Tecnécio Tc 99m/análise , Tecnécio Tc 99m Sestamibi/análise , Tomografia Computadorizada de EmissãoRESUMO
The investigation of left ventricular contractile reserve usually requires the determination of left ventricular volume, but its measurement with radionuclide angiography is difficult. The aim of this study was to determine left ventricular volume directly during exercise by the simultaneous measurement of peak exercise left ventricular ejection fraction (LVEF) and oxygen consumption (VO2max) and to compare the results with another geometric method. In the absence of lung disease, the systemic arteriovenous oxygen difference (DAVmax) during maximal exercise converges to 0.13-0.14 ml O2 per ml blood. The measurement of VO2max allows maximal cardiac output (COmax) to be calculated as VO2max = COmax. DAVmax. By simultaneously determining LVEFex, exercise end-diastolic volume (EDVex) can then be expressed as a linear function of VO2max, maximal heart rate (HRmax), DAVmax and LVEFex. Then, the relationship between end-diastolic counts and true volume can be derived at rest. The two methods were closely correlated (r = 0.91, P < 0.001), despite the geometric method being less accurate when applied to low counting statistic acquisitions. We conclude that rest and exercise left ventricular volume can be determined non-invasively by the simultaneous measurement of VO2max and LVEFex. Furthermore, this method provides additional prognostic information which is clinically relevant in the staging of patients with heart failure.
Assuntos
Coração/diagnóstico por imagem , Consumo de Oxigênio , Ventriculografia com Radionuclídeos/métodos , Adulto , Idoso , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Teste de Esforço , Imagem do Acúmulo Cardíaco de Comporta/métodos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Prognóstico , Função Ventricular EsquerdaRESUMO
The recent evolutions of the imaging modalities, the dose calculation models, the linear accelerators and the portal imaging permit to improve the quality of the conformal radiation therapy treatment planning. With DICOM protocols, the acquired imaging data coming from different modalities are treated by performant image fusion algorithms and yield more precise target volumes and organs at risk. The transformation of the clinical target volumes (CTV) to planning target volumes (PTV) can be realised using advanced probabilistic techniques based on clinical experience. The treatment plans evaluation is based on the dose volume histograms. Their precision and clinical relevance are improved by the multi-modality imaging and the advanced dose calculation models. The introduction of the inverse planning systems permitting to realise modulated intensity radiation therapy generates highly conformal dose distributions. All the previously cited complex techniques require the application of rigorous quality assurance programs.
Assuntos
Fracionamento da Dose de Radiação , Radioterapia Conformacional/métodos , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias/radioterapia , Planejamento de Assistência ao PacienteRESUMO
Although gynaecological cancers are not currently part of the clinical indications in the French registration for [18F]-fluoro-2-deoxyglucose (FDG), various studies indicate in this context a potential clinical benefit of imaging with this radiopharmaceutical and PET, a new imaging modality that can be performed either with a dedicated machine or with a "hybrid" gamma-camera (CDET). The potential indications of FDG-PET in mammary, ovarian or cervical cancers are reviewed according to the diagnostic phase: screening, tumour characterisation, staging, therapeutic follow-up and search for recurrence. By pooling the published results, the accuracy of FDG-PET could be estimated with a reasonable precision in various clinical settings: characterisation of a breast tumour (598/696 = 86%), lymph node invasion in breast cancer (525/602 = 87%), recurrence of breast cancer (114/127 = 90%), characterisation of adnexal masses (130/176 = 78%), recurrence of ovarian cancer (152/172 = 88%), lymph node invasion in cervical cancer (98/103 = 95%). Authors also present original data concerning their experience of recurrence detection with CDET in breast or ovarian cancers. In 44 patients suspicious of recurrence of breast cancer, FDG-CDET sensitivity was 94%, specificity 82% and accuracy 91%; in 18 patients suspicious of recurrence of ovarian cancer, specificity, sensitivity and accuracy were 100%. The impact of dedicated PET and CDET examinations performed by our team during year 2000, led, according to 63 forms returned to us, to a modification of stage in 48% of breast cancers, 36% of ovarian cancers, 43% of cervical cancers and above all induced a modification in patients' management in respectively 69%, 64% and 60% of cases, more than the average rate in cancer patients which was 50%. No significant difference was observed between clinical impact of dedicated PET and CDET examinations.
Assuntos
Desoxiglucose , Radioisótopos de Flúor , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Tomografia Computadorizada de Emissão , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Metástase Linfática/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias do Colo do Útero/diagnóstico por imagemRESUMO
COLORECTAL CANCERS: FDG-PET is a very effective tool in the follow-up of colorectal cancer for the early detection of recurrences, the search for other localisations in case of resectable lesions and for the evaluation of therapies. For the other digestive cancers, the data in the literature are less abundant and they do not yet have Marketing Authorization in France. OESOPHAGEAL CANCER: FDG-PET appears very promising for staging and detection of recurrences of oesophageal carcinomas. Pancreatic cancer Although the indication is difficult, FDG-PET appears superior to morphological techniques for the characterization and the locoregional staging of pancreatic tumours. BILARY AND GASTRIC CARCINOMAS: FDG-PET is promising but its role has to be confirmed in larger series for the detection of biliary and gastric carcinomas. OTHER DIGESTIVE TUMOURS: In cases of hepatocarcinoma, FDG-PET appears efficient only in cases of undifferentiated tumours, and in cases of malignant neuroendocrine digestive tumours, is useful in combination with somatostatin receptor imaging.
Assuntos
Fluordesoxiglucose F18 , Neoplasias Gastrointestinais/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão , Humanos , Sensibilidade e EspecificidadeRESUMO
A digital radioimager (RI), conventional radioautography (RA), and tracks microradioautography (MRA) were used to assess the biodistributions and kinetics of 99mTc-dimercaptosuccinic (99mTc-DMSA) and 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) in rat at both macroscopic and microscopic levels. Three groups of male Wistar rats were studied. Using gamma-counting, kidney, liver, spleen and blood kinetics of both tracers were assessed in the three groups. Using RA and RI, renal slices were analyzed in group 1 the animals being sacrified from 2 to 60 min after injection of 99mTc-MAG3, and in group 2 the animals being sacrificed from 0.5 to 24 hr after injection of 99mTc-DMSA. Using MRA, renal slices were analyzed for 99mTc-DMSA (group 3). RA films and RI images displayed the variation with time of the cortical and medullary uptakes of the tracers. No regional heterogeneity within the different structures could be seen neither with RA films nor with MRA. The remaining activity in the blood 24 hr after injection of 99mTc-DMSA was evaluated. The tissular distributions of both tracer being homogenous, mean values of cortical uptake seems to be acceptable for dosimetric studies. Our results incite to use of 99mTc-MAG3 instead of 99mTc-DMSA when both tracers may be indicated.
Assuntos
Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacocinética , Tecnécio Tc 99m Mertiatida/metabolismo , Tecnécio Tc 99m Mertiatida/farmacocinética , Animais , Autorradiografia , Córtex Renal/citologia , Córtex Renal/metabolismo , Fígado/metabolismo , Masculino , Microrradiografia , Ratos , Ratos Wistar , Baço/metabolismo , Ácido Dimercaptossuccínico Tecnécio Tc 99m/sangue , Ácido Dimercaptossuccínico Tecnécio Tc 99m/metabolismo , Tecnécio Tc 99m Mertiatida/sangue , Distribuição TecidualRESUMO
This review of the different methodologies used for animal imaging with radioactive compounds presents the most recent approaches developed for both in vitro and in vivo studies. The choice of a detector for analysis of the spatial distribution of radionuclides deposited in biological tissues results in a trade-off between the size and nature of the region to study (in vitro or in vivo), the required spatial resolution and the penetrating characteristics of the ionizing radiation. Real time detectors are now available for quantitative imaging of 2D or 3D radioactive samples and offer either an increased dynamic range or a lowered sensitivity in comparison with film radioautography. For high resolution imaging, two specific techniques are proposed for applications to rodents. The usefulness of self-triggering intensified charge coupled device (STIC) is illustrated for in vitro localization in radiotoxicological studies of alpha-emitters. For in vivo techniques, the performance of positron emission tomography (PET) is discussed, as a promising method of molecular imaging of biological processes.
Assuntos
Cintilografia/métodos , Partículas alfa , Animais , Autorradiografia/métodos , Técnicas In Vitro , Isótopos/análise , Contagem de Cintilação/métodos , Sensibilidade e Especificidade , Tomografia Computadorizada de Emissão/métodosRESUMO
BACKGROUND: Multiharmonic Fourier phase analysis of radionuclide angiography is a well-established method for the diagnosis of arrhythmogenic right ventricular cardiomyopathy. We sought to determine the optimal acquisition parameters: number of frames per cycle and number of counts per frame, with all other acquisition and processing parameters being fixed. METHODS AND RESULTS: Radionuclide angiography with list mode acquisition was performed in 10 normal subjects (pilot group) and 11 patients with arrhythmogenic right ventricular cardiomyopathy (validation group), allowing the reconstruction of electrocardiography-gated constant phase studies with different parameters: 16, 24, and 32 frames per cycle and 200, 400, 600, and 800 kcounts per frame. Three harmonics Fourier phase analysis was applied, and optimal acquisition parameters (defined as those providing best homogeneous phase distribution histogram in the pilot group) were defined as judged by the H3 right ventricular phase SD and delta 95%. These were 16 frames per cycle and 600 kcounts per frame. Then we verified in the validation group that these optimal acquisition parameters did not induce any significant relative loss of information compared with other acquisition parameters with more temporal resolution (24 and 32 frames per cycle) or more statistics (800 kcounts per frame). This result was realized by the calculation of normalized H3 right ventricular SD, right ventricular delta 95%, and (SD[left ventricle] - SD[right ventricle]). CONCLUSIONS: In practice, 16 frames per cycle and 600 kcounts per frame are optimal for multiharmonic Fourier phase analysis, with all other acquisition and processing variables being fixed as specified.
Assuntos
Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Imagem do Acúmulo Cardíaco de Comporta , Adulto , Feminino , Análise de Fourier , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Projetos Piloto , Estudos Prospectivos , Processamento de Sinais Assistido por ComputadorRESUMO
The activity of LY333328 against Enterococcus faecalis JH2-2, which is susceptible to glycopeptides, and against its transconjugants E. faecalis BM4281 and BM4316, with VanB and VanA phenotypes, respectively, was investigated. LY333328 was active in vitro against the three strains, for which MICs were 2 microg/ml on agar and 0.25 microg/ml in broth. LY333328 was bactericidal in broth against E. faecalis JH2-2 and BM4281 at a concentration of 8 microg/ml and against BM4316 at a concentration of 30 microg/ml. The protein binding of LY333328 to rabbit serum was >99%, and the bactericidal activity of LY333328 in broth was reduced when it was tested in the presence of 90% rabbit serum. Autoradiographic studies performed in rabbits with enterococcal endocarditis showed that 14[C]LY333328 was distributed heterogeneously throughout cardiac vegetations. In rabbits with aortic endocarditis, a regimen of 20 mg of LY333328 per kg of body weight administered intramuscularly twice a day for 5 days after a loading dose of 40 mg/kg was active against the three strains in vivo (P < 0.01), whereas vancomycin was not active against the VanB-type strain and teicoplanin was not active against the VanA-type strain. We conclude that the activity of LY333328 is not significantly modified by acquired resistance to glycopeptides in E. faecalis either in vitro or in experimental endocarditis.