Telmisartan, a selective angiotensin II receptor antagonist, is primarily excreted via hepatobiliary transport. The predominant contribution of organic anion transporting polypeptide (OATP) 1B3 in its hepatic uptake of telmisartan has been demonstrated by in vitro transport studies. In the present study, a quantitative positron emission tomography (PET) methodology was developed for in vivo kinetic assessment of hepatobiliary transport of telmisartan. Serial abdominal PET scans were performed in rats following intravenous administration of [(11)C]telmisartan as a radiotracer. PET scans revealed that [(11)C]telmisartan was localized primarily in the liver and some of the radioactivity moved to the intestine, which corresponds to biliary excretion. Radiometabolite analysis by radiometric HPLC showed that [(11)C]telmisartan was converted to its acylglucuronide, which was mainly detected in bile, but little in plasma and liver. Integration plot analysis revealed that [(11)C]telmisartan was taken up into the liver as rapidly as the hepatic blood flow rate, and the radiometabolite was subsequently excreted into the bile. When rifampicin, a typical Oatp inhibitor, was coadministered with [(11)C]telmisartan in rats, hepatic uptake clearance of [(11)C]telmisartan was significantly decreased, whereas biliary efflux clearance was not changed. Coinjection with unlabeled telmisartan (4 and 10 mg/kg) also decreased hepatic uptake clearance of [(11)C]telmisartan. On the other hand, PET imaging analysis revealed a significant increase of biliary efflux when telmisartan dose was increased to more than 4 mg/kg. These results suggested that the hepatic uptake of [(11)C]telmisartan mainly consists of a saturable process mediated by Oatps in rats, according to noninvasive real-time measurement of tissue radioactivity with the use of PET. The present study with rats is expected to provide the feasibility of PET imaging study to quantitatively estimate OATP1B3 function in humans.
We developed a pravastatin derivative, sodium (3R,5R)-3,5-dihydroxy-7-((1S,2S,6S,8S)-6-hydroxy-2-methyl-8-((1-[ 11 C]-(E)-2-methyl-but-2-enoyl)oxy)-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)heptanoate ([ 11 C]DPV), as a positron emission tomography (PET) probe for noninvasive measurement of hepatobiliary transport, and conducted pharmacokinetic analysis in rats as a feasibility study for future clinical study. Transport activities of DPV in freshly isolated rat hepatocytes and rodent multidrug resistance-associated protein 2 (rMrp2; human, MRP2)-expressing membrane vesicles were similar to those of pravastatin. Rifampicin diminished the uptake of DPV and pravastatin by the hepatocytes, with similar inhibition potency. [11 C]DPV underwent biotransformation to produce at least two metabolites in rat, but metabolism of [ 11 C]DPV occurred negligibly in human hepatocytes during a 90-minute incubation. After intravenous injection, [11 C]DPV was mainly distributed to the liver and kidneys, where the tissue uptake clearances (CL uptake,liver and CL uptake,kidney ) were blood-flow-limited (73.6 6 4.8 and 24.6 6 0.6 ml/min per kilogram, respectively). Systemic elimination of [ 11 C]DPV was delayed in rifampicin-treated rat and an Mrp2-deficient mutant rat, Eisai hyperbilirubinemic mutant rat (EHBR). Rifampicin treatment decreased both CL uptake,liver and CL uptake,kidney of [ 11 C]DPV by 30% (P , 0.05), whereas these parameters were unchanged in EHBR. Meanwhile, the canalicular efflux clearance (CL int,bile ) of [ 11 C]DPV, which was 12.2 6 1.5 ml/min per kilogram in the control rat, decreased by 60% and 89% in rifampicin-treated rat and EHBR (P , 0.05), respectively. These results indicate that [
Superconducting FeSe0.8Te0.2 thin films on SrTiO3, LaAlO3 and CaF2 substrates were electrochemically etched in an ionic liquid, DEME-TFSI, electrolyte with a gate bias of 5 V. Superconductivity at 38 K was observed on all substrates after the etching of films with a thickness greater than 30 nm, despite the different Tc values of 8 K, 12 K and 19 K observed before etching on SrTiO3, LaAlO3 and CaF2 substrates, respectively. Tc returned to its original value with the removal of the gate bias. The observation of Tc enhancement for these thick films indicates that the Tc enhancement is unrelated to any interfacial effects between the film and the substrate. The sheet resistance and Hall coefficient of the surface conducting layer were estimated from the gate bias dependence of the transport properties. The sheet resistances of the surface conducting layers of the films on LaAlO3 and CaF2 showed identical temperature dependence, and the Hall coefficient was found to be almost independent of temperature and to take values of −0.05 to −0.2 m2/C, corresponding to 4–17 electrons per FeSe0.8Te0.2 unit cell area in two dimensions. These common transport properties on various substrates suggest that the superconductivity at 38 K appears in the surface conducting layer as a result of an electrochemical reaction between the surface of the FeSe0.8Te0.2 thin film and the ionic liquid electrolyte.
We report deep-red long-lasting persistent luminescence in Cr3+-doped LaAlO3 perovskite phosphor synthesized by solid-state reaction. The LaAlO3:Cr3+ sample showed persistent luminescence peaking at a very long wavelength of 734 nm due to Cr3+:2E → 4A2 transition after ultraviolet excitation. The Sm3+ ion was found to be a good codopant for increasing the persistent luminescence intensity more than 35-fold. For the Cr3+–Sm3+-codoped LaAlO3 sample, the radiance of persistent luminescence in mW sr−1 m−2 unit was higher than or comparable to that of ZnGa2O4:Cr3+ phosphor, which is a candidate phosphor with a peak luminescence at 694 nm for in vivo imaging application.
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