RESUMEN
BACKGROUND: Several factors may decrease the accuracy of quantitative PET myocardial perfusion imaging (MPI). It is therefore essential to ensure that myocardial blood flow (MBF) values are reproducible and accurate, and to design systematic protocols to achieve this. Until now, no systematic phantom protocols have been available to assess the technical factors affecting measurement accuracy and reproducibility in MPI. MATERIALS AND METHODS: We implemented a standard measurement protocol, which applies a flow phantom in order to compare image-derived flow values with respect to a ground truth flow value with [15O]H2O MPI performed on both a Discovery MI (DMI-20, GE Healthcare) and a Biograph Vision 600 (Vision-600, Siemens Healthineers) system. Both systems have automatic [15O]H2O radio water generators (Hidex Oy) individually installed, allowing us to also study the differences occurring due to two different bolus delivery systems. To investigate the technical factors contributing to the modelled flow values, we extracted the [15O]H2O bolus profiles, the flow values from the kinetic modeling (Qin and Qout), and finally calculated their differences between test-retest measurements on both systems. RESULTS: The measurements performed on the DMI-20 system produced Qin and Qout values corresponging to each other as well as to the reference flow value across all test-retest measurements. The repeatability differences on DMI-20 were 2.1% ± 2.6% and 3.3% ± 4.1% for Qin and Qout, respectively. On Vision-600 they were 10% ± 8.4% and 11% ± 10% for Qin and Qout, respectively. The measurements performed on the Vision-600 system showed more variation between Qin and Qout values across test-retest measurements and exceeded 15% difference in 7/24 of the measurements. CONCLUSIONS: A preliminary protocol for measuring the accuracy and reproducibility of flow values in [15O]H2O MPI between digital PET/CT systems was assessed. The test-retest reproducibility falls below 15% in majority of the measurements conducted between two individual injector systems and two digital PET/CT systems. This study highlights the importance of implementing a standardized bolus injection and delivery protocol and importance of assessing technical factors affecting flow value reproducibility, which should be carefully investigated in a multi-center setting.
RESUMEN
Ochratoxin A (OTA) is one of the most frequent mycotoxins detected in human blood worldwide. Apart from its well known nephrotoxicity, OTA-induced teratogenicity and carcinogenicity proven in animals are potential effects also in humans. Pregnant women have been exposed to this food contaminant via dietary exposure in a continuous and widespread manner. Although the transplacental transfer of OTA has been demonstrated in laboratory animals and the presence of OTA in human fetal samples has been reported, little is known about the role of human placenta in OTA toxicokinetics. In this study, human perfused placenta was used to reveal the actual placental toxicokinetics of OTA using concentrations found in serum of pregnant women. Moreover, the effect of protein concentration and biological significance of placental transporters on the OTA transfer in human placenta were also determined. Our study is the first to pursue the transfer of OTA through perfused human placenta. The transfer of OTA through term human placenta was barely detectable in all perfusions. Inhibitors of neither ABCG2 nor ABCC2 increased the transport of OTA to fetal circulation in placental perfusion, and thus these transporters apparently do not have biological significance in inhibiting transplacental transfer of OTA. Human albumin has inhibited OTA transfer through a tight monolayer of BeWo b30 cells. Finding from this study clearly contradict the existing epidemiological studies reporting higher OTA levels in fetal than in maternal circulation in vivo.
Asunto(s)
Carcinógenos/farmacocinética , Ocratoxinas/farmacocinética , Placenta/metabolismo , Teratógenos/farmacocinética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/metabolismo , Albúminas/metabolismo , Proteínas Portadoras/metabolismo , Línea Celular , Femenino , Humanos , Técnicas In Vitro , Intercambio Materno-Fetal , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Proteínas de Neoplasias/metabolismo , Transportadores de Anión Orgánico Sodio-Independiente/metabolismo , Perfusión , EmbarazoRESUMEN
Aflatoxin B1 (AFB1), a common dietary contaminant, is a major risk factor of hepatocellular carcinoma (HCC). Early onset of HCC in some countries in Africa and South-East Asia indicates the importance of early life exposure. Placenta is the primary route for various compounds, both nutrients and toxins, from the mother to the fetal circulation. Furthermore, placenta contains enzymes for xenobiotic metabolism. AFB1, AFB1-metabolites, and AFB1-albumin adducts have been detected in cord blood of babies after maternal exposure during pregnancy. However, the role that the placenta plays in the transfer and metabolism of AFB1 is not clear. In this study, placental transfer and metabolism of AFB1 were investigated in human placental perfusions and in in vitro studies. Eight human placentas were perfused with 0.5 or 5microM AFB1 for 2-4 h. In vitro incubations with placental microsomal and cytosolic proteins from eight additional placentas were also conducted. Our results from placental perfusions provide the first direct evidence of the actual transfer of AFB1 and its metabolism to aflatoxicol (AFL) by human placenta. In vitro incubations with placental cytosolic fraction confirmed the capacity of human placenta to form AFL. AFL was the only metabolite detected in both perfusions and in vitro incubations. Since AFL is less mutagenic, but putatively as carcinogenic as AFB1, the formation of AFL may not protect the fetus from the toxicity of AFB1.