Ying-Cheng Huang

Phase evolution of co-precipitated Bi–Pb–Sr–Ca–Cu–O powder

Abstract The evolution of the phase formation in (Bi,Pb)–Sr–Ca–Cu–O superconducting materials prepared by the co-precipitation method has been investigated by X-ray diffraction analysis. Formation of the desired 2223 phase was found to proceed through a complicated reaction route of forming the single, double and triple Cu–O layered superconducting structures in sequence with increasing temperature. The phase with a more Cu–O layered structure was found to grow at the expense of the less Cu–O layered phase. Several intermediate phases of Bi–Sr/Ca–O compounds were found to be closely related to the formation of the superconducting phase with single and double Cu–O layered structures. The investigation of the kinetics of forming the 2223 phase revealed that two mechanisms dominated the reaction rate in the early and late stages of growing the 2223 phase.

Synthesis and evaluation of [18F]Fluorobutyl ethacrynic amide: a potential PET tracer for studying glutathione transferase.

[(18)F]Flurobutyl ethacrynic amide ([(18)F]FBuEA) was prepared from the precursor tosylate N-Boc-N-[4-(toluenesulfonyloxy)butyl]ethacrynic amide with a radiochemical yield of 3%, a specific activity of 48 GBq/μmol and radiochemical purity of 98%. Chemical conjugation of [(18)F]FBuEA with glutathione (GSH) via a self-coupling reaction and enzymatic conjugation under catalysis of glutathiontransferase alpha (GST-α) and π provided about 41% yields of radiochemical conjugated product [(18)F]FBuEA-GSH, 85% and 5-16%, respectively. The catalytic selectivity of this tracer toward GST-alpha was addressed. Positron emission tomography (PET) imaging of [(18)F]FBuEA in normal rats showed that a homogeneous pattern of radioactivity was distributed in the liver, suggesting a catalytic role of GST. By contrast, PET images of [(18)F]FBuEA in rats with thioacetamide-induced cholangiocarcinoma displayed a heterogeneous pattern of radioactive accumulation with cold spots in tumor lesions. PET imaging with [(18)F]FBuEA could be used for early diagnosis of hepatic tumor with a low GST activity as well as liver function.

Effects of powder calcination on the properties of Bi-2223 tape

The effects of powder calcination on the properties of Bi-2223 tape have been investigated. The transport property of the tape was found to depend strongly on the condition for powder calcination. The tape fabricated with powder calcined at lower temperature resulted in a microstructure with a larger grain size and higher transport critical current. The development of the microstructure of the tape in the subsequent heat-treatment process is correlated with the constituents in the starting powder. The magnetization of samples characterized by SQUID indicates that the magnetic property is also correlated to the microstructures of the tape. An anomalous flux disturbance occurring at 70 K was observed on the zero-field cooling curves of all samples.

18F-glutathione conjugate as a PET tracer for imaging tumors that overexpress L-PGDS enzyme.

Lipocalin-type prostaglandin D synthase (L-PGDS) has been correlated with the progression of neurological disorders. The present study aimed at evaluating the imaging potency of a glutathione conjugate of fluorine-18-labeled fluorobutyl ethacrynic amide ([18F]FBuEA-GS) for brain tumors. Preparation of [18F]FBuEA-GS has been modified from the -4-tosylate derivative via radiofluorination in 5% radiochemical yield. The mixture of nonradioactive FBuEA-GS derived from a parallel preparation has be resolved to two isomers in a ratio of 9∶1 using analytic chiral reversed phase high performance liquid chromatography (RP-HPLC). The two fluorine-18-labeled isomers purified through nonchiral semipreparative RP-HPLC as a mixture were studied by assessing the binding affinity toward L-PGDS through a gel filtration HPLC, by analyzing radiotracer accumulation in C6 glioma cells, and by evaluating the imaging of radiotracer in a C6 glioma rat with positron emission tomography. The inhibition percentage of the production of PGD2 from PGH2 at the presence of 200 µM of FBuEA-GS and 4-Dibenzo[a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)butyl]piperidine (AT-56) were 74.1±4.8% and 97.6±16.0%, respectively. [18F]FBuEA-GS bound L-PGDS (16.3–21.7%) but not the isoform, microsomal prostaglandin E synthase 1. No binding to GST-alpha and GST-pi was observed. The binding strength between [18F]FBuEA-GS and L-PGDS has been evaluated using analytic gel filtration HPLC at the presence of various concentrations of the cold competitor FBuEA-GS. The contrasted images indicated that the radiotracer accumulation in tumor lesions is probably related to the overexpression of L-PGDS.

Microstructural evolution and the role of Pb atmosphere in forming Bi-2223 superconductor

Abstract The evolution of microstructures during the phase conversion for the Bi(Pb)SrCaCuO system has been studied for specimens with cumulative sintering. The changes of surface morphology, crystallinity, composition, weight and diameter were characterized for specimens sintered iteratively at a fixed temperature. Evaporation of Pb from the surface was found to result in a microstructural variation between surface and interior of specimens. The phase conversion for the sintered specimen was significantly enhanced by sintering the specimen with fresh powder pellet of the same composition. The enhancement is attributed to the change of Pb atmosphere during sintering treatment.

Synthesis and characterization of boron fenbufen and its F-18 labeled homolog for boron neutron capture therapy of COX-2 overexpressed cholangiocarcinoma

Abstract Boron neutron capture therapy (BNCT) is a binary therapy that employs neutron irradiation on the boron agents to release high‐energy helium and alpha particles to kill cancer cells. An optimal response to BNCT depends critically on the time point of maximal 10B accumulation and highest tumor to normal ratio (T/N) for performing the neutron irradiation. The aggressive cholangiocarcinoma (CCA) representing a liver cancer that overexpresses COX‐2 enzyme is aimed to be targeted by COX‐2 selective boron carrier, fenbufen boronopinacol (FBPin). Two main works were performed including: 1) chemical synthesis of FBPin as the boron carrier and 2) radiochemical labeling with F‐18 to provide the radiofluoro congener, m‐[18F]fluorofenbufen ester boronopinacol (m‐[18F]FFBPin), to assess the binding affinity, cellular accumulation level and distribution profile in CCA rats. FBPin was prepared from bromofenbufen via 3 steps with 82% yield. The binding assay employed [18F]FFBPin to compete FBPin for binding to COX‐1 (IC50 = 0.91 ± 0.68 &mgr;M) and COX‐2 (IC50 = 0.33 ± 0.24 &mgr;M). [18F]FFBPin‐derived 60‐min dynamic PET scans predict the 10B‐accumulation of 0.8–1.2 ppm in liver and 1.2–1.8 ppm in tumor and tumor to normal ratio = 1.38 ± 0.12. BNCT was performed 40–55 min post intravenous administration of FBPin (20–30 mg) in the CCA rats. CCA rats treated with BNCT display more tumor reduction than that by NCT with respect of 2‐[18F]fluoro‐2‐deoxy glucose uptake in the tumor region of interest, 20.83 ± 3.00% (n = 12) vs. 12.83 ± 3.79% (n = 10), P = 0.05. The visualizing agent [18F]FFBPin resembles FBPin to generate the time‐dependent boron concentration profile. Optimal neutron irradiation period is thus determinable for BNCT. A boron‐substituted agent based on COX‐2‐binding features has been prepared. The moderate COX‐2/COX‐1 selectivity index of 2.78 allows a fair tumor selectivity index of 1.38 with a mild cardiovascular effect. The therapeutic effect from FBPin with BNCT warrants a proper COX‐2 targeting of boron NSAIDs. Graphical abstract Figure. No Caption available.

Investigation of brain tumors using (18)F-fluorobutyl ethacrynic amide and its metabolite with positron emission tomography.

To date, imaging of malignant glioma remains challenging. In positron emission tomography-related diagnostic imaging, differential tumor uptake of 3′-deoxy-3′-[18F] fluorothymidine ([18F]FLT) has been shown to reflect the levels of cell proliferation and DNA synthesis. However, additional biomarkers for tumors are urgently required. Aberrant levels of glutathione transferase (GST) activity have been hypothesized to constitute such a novel diagnostic marker. Here, a C6 rat glioma tumor model was used to assess the ability of the positron emission tomography tracers, [18F]FLT and 18F-fluorobutyl ethacrynic amide ([18F]FBuEA), to indicate reactive oxygen species-induced stress responses as well as detoxification-related processes in tumors. Using a GST activity assay, we were able to demonstrate that FBuEA is more readily catalyzed by GST-π than by GST-α. Furthermore, we showed that FBuEA-GS, a metabolite of FBuEA, elicits greater cytotoxicity in tumor cells than in normal fibroblast cells. Finally, in vitro and in vivo investigation of radiotracer distribution of [18F]FBuEA and [18F] FBuEA-GS revealed preferential accumulation in C6 glioma tumor cells over normal fibroblast cells for [18F]FBuEA-GS but not for [18F]FBuEA.

Synthesis of YBa2Cu4Oy powder by the EDTA solution method and oxine coprecipitation under ambient pressure

Abstract The YBa 2 Cu 4 O y superconducting powder were synthesized by the ethylene-diamine-tetra-acetic (EDTA) precursor solution method and 8-hydroxyquinoline-triethylamine coprecipitation. Pure 124 phase can be obtained through repeated heat treatment at 800°C in flowing oxygen. The effects of heat treatment temperature and sintering time were investigated.

Synthesis and evaluation of ortho -[ 18 F]fluorocelecoxib for COX-2 cholangiocarcinoma imaging

Background An 18F-tagged NSAID analog was prepared for use as a probe for COX-2 expression, which is associated with tumor development. Methods The in vivo uptake of celecoxib was monitored with ortho-[18F]fluorocelecoxib using positron emission tomography (PET). The binding affinity of ortho-[18F]fluorocelecoxib to COX-1 and COX-2 enzymes were assessed using the competitor celecoxib. Results The IC50 values were 0.039 μM and 0.024 μM, respectively. A selectivity index of 1.63 was obtained (COX-2 vs COX-1). COX-2 overexpressed cholangiocarcinoma (CCA) murine cells took up more ortho-[18F]fluorocelecoxib than that by usual CCA cells from 10 to 60 minutes post incubation. Competitive inhibition (blocking) of the tracer uptake of ortho-[18F]fluorocelecoxib in the presence of celecoxib by the COX-2 overexpressed CCA cells and the usual CCA cells gave the IC50 values of 0.5 μM and 46.5 μM, respectively. Based on the in vitro accumulation data and in vivo metabolism half-life (30 min), PET scanning was performed 30–60 min after the administration of ortho-[18F]fluorocelecoxib through the tail vein. Study of ortho-[18F]F-celecoxib in the CCA rats showed a tumor to normal ratio (T/N) of 1.38±0.23 and uptake dose of 1.14±0.25 (%ID/g). Conclusion The inferior in vivo blocking results of 1.48±0.20 (T/N) and 1.18±0.22 (%ID/g) suggests that the nonspecificity is associated with the complex role of peroxidase or the binding to carbonic anhydrase.

Dataset on the synthesis and characterization of boron fenbufen and its F-18 labeled homolog

The data presented in this article are related to the research article entitled “Synthesis and Characterization of Boron Fenbufen and its F-18 Labeled Homolog for Boron Neutron Capture Therapy of COX-2 Overexpressed Cholangiocarcinoma”. The contents of the data article include 1) the set up for performing in vitro binding assay, 2) 1H-, 13C- and 19F-NMR of compounds described in main text, 3) HPLC chromatogram of the fluorination mixtures, 4) data of in vitro stability test, cell survival assay, western blot and PCR analysis, 5) the modules for fixing the two CCA rats for BNCT, and 6) bar diagram for tumor reduction using [18F]FDG-PET 24 h post treatment with BNCT.