In the past Yearn Seong Choe has collaborated on articles with Wenjun Miao and Choong Mo Kang. One of their most recent publications is Safety and tumor tissue accumulation of pegylated graphene oxide nanosheets for co-delivery of anticancer drug and photosensitizer. Which was published in journal Biomaterials.

More information about Yearn Seong Choe research including statistics on their citations can be found on their Copernicus Academic profile page.

Yearn Seong Choe's Articles: (11)

Safety and tumor tissue accumulation of pegylated graphene oxide nanosheets for co-delivery of anticancer drug and photosensitizer

AbstractHere, we report the safety, tumor accumulation and potential of polyethylene glycol-grafted graphene oxide (pGO) as a multimodal nanocarrier of photosensitizers and synergistic anticancer agents. First, both graphene oxide (GO) and pGO were synthesized, and their in vitro and in vivo toxicities were tested. When 80 mg/kg was injected intravenously into mice, there was 100% fatality in the GO-treated group, but 100% survival among mice treated with pGO nanosheets. Treatment of cells with a photosensitizer chlorin e6 (Ce6) in pGO nanophysisorplexes significantly enhanced cellular delivery compared to that seen with Ce6 alone. The combination and dose reduction indexes revealed that combining doxorubicin (Dox) with Ce6 with at a molar ratio of 1:2 provided the highest synergism. The Ce6- and Dox-loaded pGO nanophysisorplexes (Ce6/Dox/pGO) were 148.0 ± 18.0 nm in size. Molecular imaging of mice showed that Ce6/Dox/pGO could accumulate in tumor tissues over 3 days. Moreover, in SCC tumor-bearing mice, the photodynamic anticancer effects of Ce6/Dox/pGO were higher than those of Ce6/pGO or Dox/pGO. Moreover, tumor sections from illuminated mice treated with Ce6/Dox/pGO showed substantial disruption of tumor nuclei, whereas the other groups did not. Our results suggest that pGO nanosheets have superior in vivo safety relative to GO, and that it is possible to enhance the tumor tissue distribution and photodynamic anticancer effects of systemically administered Ce6 by forming multimodal nanophysisorplexes with pGO and synergistic anticancer chemotherapeutics such as Dox.

A vascular endothelial growth factor 121 (VEGF121)-based dual PET/optical probe for in vivo imaging of VEGF receptor expression

AbstractWe have developed a vascular endothelial growth factor 121 (VEGF121)-based, dual positron emission tomography (PET)/optical imaging probe for monitoring VEGF receptor (VEGFR) expression using a streptavidin (SAv)–biotin platform. 64Cu-1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid (DOTA)-conjugated Alexa Fluor 680 (AF)-SAv/biotin-PEG-VEGF121 (64Cu-labeled dual probe) was prepared with a radiochemical yield of 31.40 ± 3.30% and was stable for 24 h in serum. A human aortic endothelial cell binding study showed avid, time-dependent cellular uptake of the 64Cu-labeled dual probe. MicroPET imaging of U87MG tumor-bearing mice injected with 64Cu-labeled dual probe showed rapid, high accumulation of radioactivity in tumors, which reached 3.90 ± 0.17 %ID/g and 4.93 ± 0.80 %ID/g at 1 and 22 h after injection, respectively. Subsequent optical imaging of mice revealed strong fluorescence signals in tumors. Biodistribution studies performed after in vivo imaging demonstrated tumor uptake of 4.19 ± 0.14 %ID/g. Tumor uptake was blocked by 28% in the presence of VEGF121, confirming the VEGFR specificity of the 64Cu-labeled dual probe. Ex vivo microPET images of major tissues showed the signal intensities consistent with optical images of the corresponding tissues. Moreover, it was shown that tumor uptake of the 64Cu-labeled dual probe was not due to non-specific uptake by 64Cu-DOTA-conjugated AF-SAv (tumor uptake; 1.57 ± 0.09 %ID/g). Taken together, these results suggest that the 64Cu-labeled dual probe is a promising candidate for dual PET/optical imaging of VEGFR expression.

Regular articleHippocampal volume and shape in pure subcortical vascular dementia

AbstractThe purposes of the present study were to explore whether hippocampal atrophy exists in pure subcortical vascular dementia (SVaD) as defined by negative 11C-Pittsburg compound-B (PiB−) positron emission tomography and to compare hippocampal volume and shape between PiB− SVaD and PiB positive (PiB+) Alzheimer's disease (AD) dementia. Hippocampal volume and shape were compared among 40 patients with PiB− SVaD, 34 with PiB+ AD, and 21 elderly with normal cognitive function (NC). The normalized hippocampal volume of PiB− SVaD was significantly smaller than NC but larger than that of PiB+ AD (NC > PiB− SVaD > PiB+ AD). Both PiB− SVaD and PiB+ AD patients had deflated shape changes in the cornus ammonis (CA) 1 and subiculum compared with NC. However, direct comparison between PiB− SVaD and PiB+ AD demonstrated more inward deformity in the subiculum of the left hippocampus in PiB+ AD. PiB− SVaD patients did have smaller hippocampal volumes and inward shape change on CA 1 and subiculum compared with NC, suggesting that cumulative ischemia without amyloid pathology could lead to hippocampal atrophy and shape changes.

Synthesis and evaluation of fluorine-substituted 1H-pyrrolo[2,3-b]pyridine derivatives for dopamine D4 receptor imaging

AbstractSeven fluorine-substituted 1H-pyrrolo[2,3-b]pyridine derivatives were synthesized based on a lead ligand, 3-[[4-(4-iodophenyl)piperazin-1-yl]-methyl]-1H-pyrrolo[2,3-b]pyridine (L-750,667) and evaluated as potential dopamine D4 receptor imaging agents by positron emission tomography (PET). Binding affinities of these ligands for the dopamine D2, D3, and D4 receptor subtypes were measured in vitro. Most ligands showed high and selective binding for the D4 receptor. Ligand 7 had high affinity for the D4 receptor, whereas ligands 1, 2, and 6 showed high selectivity for the D4 receptor. Log P values were calculated for the ligands in this series and ligand 6 had the lowest lipophilicity. 18F-labeled ligand 7 demonstrated a uniform regional brain distribution and a rapid washout in mice, probably due to nonspecific binding. Based on their in vitro binding properties and calculated log P values, ligand 6 appears to have the most promise for dopamine D4 receptor imaging.

Evaluation of 4-[18F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds

AbstractClick chemistry is a useful approach for the preparation of novel radiopharmaceuticals. In this study, we evaluated 4-[18F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds. Our results showed that nucleophilic substitution of 4-tosyloxy-1-butyne with K[18F]F produces vinyl acetylene as well as 4-[18F]fluoro-1-butyne, while the same reaction using 5-tosyloxy-1-pentyne gives exclusively 5-[18F]fluoro-1-pentyne. Thus, ω-[18F]fluoro-1-alkynes with chain lengths longer than four carbons may be better radiolabeled synthons for use in click chemistry.

Original articlesSyntheses and biological evaluation of 18F-labeled 3-(1-benzyl-piperidin-4-yl)-1-(1-methyl-1H-indol-3-yl)propan-1-ones for in vivo mapping of acetylcholinesterase

AbstractWe synthesized novel 18F-labeled acetylcholinesterase (AChE) inhibitors, 3-[1-(3- and 4-[18F]fluoromethylbenzyl)piperidin-4-yl]-1-(1-methyl-1H-indol-3-yl)propan-1-ones ([18F]1 and [18F]2) and 3-[1-(4-[18F]fluorobenzyl)piperidin-4-yl]-1-(1-methyl-1H-indol-3-yl)propan-1-one ([18F]3) in high yields (decay-corrected, 25%–40%) and with high effective specific activities (>37 GBq/μmol). Tissue distribution studies of the [18F]1 and the [18F]3 in mice showed the nonspecific bindings in brain regions, with metabolic defluorination of the [18F]1. The result suggests that these radioligands may not be suitable agents for in vivo mapping of AChE, despite their potent in vitro anti-AChE activities.

Synthesis and biological evaluation of 1-(4-[18f]fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine for in vivo studies of acetylcholinesterase

AbstractWe synthesized and evaluated 1-(4-fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine (4-FDP), which is an analog of donepezil. The 4-[18F]FDP was prepared by reductive alkylation of debenzylated donepezil with 4-[18F]fluorobenzaldehyde in high radiochemical yield (decay-corrected, 40–52%) and with high effective specific activity (30–38 GBq/μmol). Tissue distribution studies in mice demonstrated nonspecific distribution of the 4-[18F]FDP in brain regions, suggesting that this radioligand may not be a suitable agent for in vivo studies of acetylcholinesterase (AChE), despite its potent in vitro biological activity.

A new nucleophilic fluorine-18 labeling method for aliphatic mesylates: reaction in ionic liquids shows tolerance for water

AbstractDownload full-size image Nucleophilic [18F]fluorination of some halo- and mesyloxyalkanes to the corresponding [18F]fluoroalkanes with fluoride-18 obtained from an 18O(p,n) [18F]F reaction, using an ionic liquid as a reaction medium, has been studied as a new method for fluorine-18 labeling. Of the various ionic liquids, 1-butyl-3-methylimidazolium triflate ([bmim][OTf]) in the presence of Cs2CO3, gave the highest radiochemical yields. This method is rapid and particularly convenient because [18F]fluoride in H2O can be added directly to the reaction media, obviating the careful drying that is typically required for currently used radiofluorination methods. As a model reaction, [18F]fluorination of 2-(3-methanesulfonyloxypropoxy)naphthalene [1] was found to provide the corresponding [18F]fluoro product in 93±1.2% (n=3) radiochemical yield, after reaction at 120 oC for 5-10 min under optimized conditions. Thus, we anticipate that this method will be very useful in the labeling of various molecules with [18F]fluoride in a convenient manner.

Synthesis and evaluation of 4-[18F]fluorothalidomide for the in vivo studies of angiogenesis

AbstractIn this study, we prepared 2-(2,6-dioxopiperidin-3-yl)-4-[18F]fluoroisoindole-1,3-dione (4-[18F]fluorothalidomide; [18F]1) for the in vivo studies of angiogenesis. Radiochemical synthesis of [18F]1 was carried out by labeling 4-trimethylammoniumthalidomide trifluoromethanesulfonate with nBu4N[18F]F in dimethyl sulfoxide (DMSO), followed by reverse-phase HPLC purification. Decay-corrected radiochemical yield of [18F]1 was 50–60%, with an effective specific activity of 42–120 GBq/μmol (end of synthesis). Incubation of the radioligand with human umbilical vein endothelial cells (HUVEC-C; American Type Culture Collection) showed a time-dependent increase in the uptake of the radioligand, and the uptake was inhibited by 8–11% in the presence of 10 μM thalidomide, indicating nonspecific binding of the radioligand. Positron emission tomography (PET) images of mice implanted with tumors in their right flanks revealed a marked accumulation of radioactivity in the livers, kidneys and bladders of the mice, and brain uptake appeared at approximately 40 min after injection. However, no radioactivity uptake was detected in the implanted tumor. Thin-layer chromatography (TLC), HPLC and LC-MS analyses of mouse liver microsomal metabolites of [18F]1 and 1 with or without nicotinamide adenine dinucleotide phosphate (NADPH) clearly revealed that the radioligand did not go through metabolic activation but underwent nonenzymatic hydrolysis at physiological pH. Therefore, these results would appear to indicate that [18F]1 may not be suitable for the in vivo studies of angiogenesis at least in mice, although it was reported that thalidomide and/or its hydrolysis products may be responsible for its activity in humans.

EGF receptor targeted tumor imaging with biotin-PEG-EGF linked to 99mTc-HYNIC labeled avidin and streptavidin

AbstractIntroductionAs direct radiolabeled peptides suffer limitations for in vivo imaging, we investigated the usefulness of radioloabeled avidin and streptavidin as cores to link peptide ligands for targeted tumor imaging.MethodsHuman epidermal growth factor (EGF) was site specifically conjugated with a single PEG-biotin molecule and linked to 99mTc-HYNIC labeled avidin-FITC (Av) or streptavidin-Cy5.5 (Sav). Receptor targeting was verified in vitro, and in vivo pharmacokinetic and biodistribution profiles were studied in normal mice. Scintigraphic imaging was performed in MDA-MB-468 breast tumor xenografted nude mice.ResultsWhereas both 99mTc-Av-EGF and 99mTc-Sav-EGF retained receptor-specific binding in vitro, the two probes substantially diverged in pharmacokinetic and biodistribution behavior in vivo. 99mTc-Av-EGF was rapidly eliminated from the circulation with a T1/2 of 4.3 min, and showed intense hepatic accumulation but poor tumor uptake (0.6%ID/gm at 4 h). 99mTc-Sav-EGF displayed favorable in vivo profiles of longer circulation (T1/2β, 51.5 min) and lower nonspecific uptake that resulted in higher tumor uptake (3.8 %ID/gm) and clear tumor visualization at 15 h.Conclusion99mTc-HYNIC labeled streptavidin linked with growth factor peptides may be useful as a protein-ligand complex for targeted imaging of tumor receptors.

Molecular mechanism of 18F-FDG uptake reduction induced by genipin in T47D cancer cell and role of uncoupling protein-2 in cancer cell glucose metabolism☆

AbstractIntroductionCompounds that modulate cancer cell glucose metabolism could open new opportunities for antitumor therapy and for monitoring response using 18F-FDG PET. Genipin, a natural dietary compound that blocks uncoupling protein 2 (UCP2)-mediated mitochondrial proton leakage, is a potential anticancer agent. We investigated the effect of genipin on glucose metabolism and the mitochondrial function of cancer cells.MethodsBreast and colon cancer cells were assessed for effects of genipin on 18F-FDG uptake. T47D breast cancer cells were further evaluated for time-dependent and dose-dependent effects on 18F-FDG uptake, lactate release, oxygen consumption rate (OCR), reactive oxygen species (ROS) production, and mitochondrial membrane potential. The effects of UCP2 knockdown were evaluated using specific siRNA.ResultsCancer cells displayed significant reductions in 18F-FDG uptake by genipin. T47D cells showed the greatest reduction to 32.6 ± 1.0% of controls by 250 μM genipin. The effect occurred rapidly, reaching a plateau by 1 h that lasted up to 24 h. The effect was dose-dependent with a half-inhibitory concentration of 60.8 μM. An accompanying decrease in lactate release was consistent with reduced glycolytic flux. OCR was significantly decreased by genipin to 82.2 ± 11.4% of controls, and ROS generation was increased to 156.7 ± 16.0%. These effects were largely reproduced by UCP2 knockdown with specific siRNA.ConclusionsGenipin decreased cancer cell 18F-FDG uptake by reducing both glycolytic flux and mitochondrial oxidative respiration. This effect appeared to occur by blocking the ability of UCP2 to dissipate energy and restrict ROS production through proton leakage.

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