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Policosanol is a hypocholesterolemic derived from sugar cane and corn that downregulates blood cholesterol levels. It can further lower blood pressure and reduce liver inflammation. Policosanol can also affect vascular calcification, however, its molecular mechanisms are not well understood. This study investigated the effect of policosanol on vascular calcification and its molecular mechanism. Policosanol decreased the expression of inorganic phosphate (Pi)-induced osteogenic genes such as distal-less homeobox 5 (Dlx5) and runt-related transcription factor 2 (Runx2). In addition, following policosanol treatment, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation increased in a time-dependent manner. The constitutively active form of AMPK (CA-AMPK) dramatically suppressed Pi-induced Dlx5 and Runx2 protein levels. Inactivation of AMPK using compound C (Com. C; AMPK inhibitor) recovered policosanol-suppressed Alizarin Red S staining levels. Insulin-induced genes (INSIGs) were induced by CA-AMPK, their overexpression suppressed Pi-induced Dlx5 and Runx2 expression. Taken together, the results demonstrate that policosanol inhibits Pi-induced vascular calcification by regulating AMPK-induced INSIG expression in vascular smooth muscle cells.

Purpose Basal metabolic rate (BMR) is an indicator of overall body metabolism and may portend unique aberrations in urine physico-chemistry and stone recurrence. The present study examined the effect of predicted BMR on 24 hours urinary metabolic profiles and stone recurrence in obese stone patients. Materials and Methods Data from 308 obese patients (body mass index [BMI] ≥30 kg/m2) diagnosed with urinary stone disease between 2003 and 2015 were analyzed retrospectively. BMR was calculated using the Harris–Benedict equation, and patients were classified into two predicted BMR categories (, Graphical Abstract

For efficient polymer gel electrolytes (PGEs) in quasi-solid-state dye-sensitized solar cells (QSS-DSSCs), six ABA triblock copolymers based on (poly(acrylonitrile-co-N-(isobutoxymethyl)acrylamide)...

The molecular weights and structural properties of polymers play key roles in the efficiency of gelators in polymer gel electrolytes (PGEs) for quasi-solid-state dye-sensitized solar cells (QSS-DSSCs). To find an appropriate gelator, we synthesized well-defined poly(acrylonitrile-co-N,N-dimethylacrylamide)-block-poly(ethylene glycol)-block-poly(acrylonitrile-co-N,N-dimethylacrylamide) ABA triblock copolymers with various molecular weights and copolymer compositions by reversible addition-fragmentation chain-transfer polymerization. The ratio of acrylonitrile (AN)/N,N-dimethylacrylamide (DMAA) in the triblock copolymers influences their solubility in liquid electrolytes (LEs) and thermal stability. The highest thermal stability was up to 360 °C, and this was achieved by the polymer with an AN/DMAA ratio of ≤4. The thermal stability was related to excessive randomness in the P(AN-co-DMAA) block that hinders cyclization among nitrile groups. Both the molecular weights and the AN/DMAA ratios enabled gel formation by controlling the amount of the polymer, and hence, they influence the ionic conductivity and diffusion as well. Based on the electrochemical properties, polymers with molecular weights above 100 kg/mole were efficient as PGEs in QSS-DSSCs. The overall power conversion efficiency (PCE) of 14 wt % SGT-626 PGE-based QSS-DSSCs was 9.72% under AM 1.5G solar illumination, comparable with an overall PCE of 9.79% for LE DSSCs. The overall PCE of the QSS-DSSCs further increased to 10.02% by incorporating 3 wt % TiO2 nanoparticles in the 14 wt % SGT-626 PGE. The SGT-626 PGE-based QSS-DSSC was also tested under indoor light conditions, and the best PCE of 21.26% was achieved under a white LED light of 1000 lux, which is higher than the PCE of 19.94% for the LE DSSC. The long-term device stability test under adverse conditions (50 °C and 1 sun illumination) reveals the improved stability of PGE-based QSS-DSSCs over LE DSSCs. In terms of PCE and long-term device stability, our PGE QSS-DSSCs have great potential over LE DSSCs for future indoor and outdoor applications.

Manufacturing temperatures of severely cold-drawn hyper-eutectoid steel wires are sufficiently high to influence the mobility of dislocations and alloy elements, thereby affecting the materials’ mechanical properties. Herein, we describe the evolution of microstructure and tensile strength of the as-drawn 3.45 GPa steel wire during post-deformation annealing for 30 min at 150−450 °C. Annealing at 150 °C raised the strength to 3.77 GPa by age-hardening through activation of dislocations pinning by carbon, while further temperature rising up to 450 °C caused a severe loss of strength. It was proved that annealing at 300 and 450 °C destabilizes the lamellar microstructure, promoting the formation of carbon-deficient (Fe,Mn,Cr)3C-type cementite particles with preferentially rounded and partially faceted hetero-interfaces. Annealing at 450 °C yielded the accumulation of Mn and Cr at the ferrite/particle interfaces, and their concentrations at the interfaces were dependent on the interface structure; i.e., lower concentrations at rounded interfaces (formed through capillarity–driven coarsening of the spheroidized cementite), and higher concentrations at faceted interfaces (that are initially existing in the as-drawn state). Our proof-of-principle observations, supported by thermodynamic calculations and kinetic assessments, provide a pathway for understanding the changes in microstructural and tensile properties during manufacturing of the hyper-eutectoid steel wires.

This study investigated the kind of seed dormancy and seed germination of Gentiana&nbsp, triflora var. japonica (Kusn.) H. Hara for developing a seed propagation method. The seeds were collected in October 2020 from plants at Mt. Sobaeksan, Korea. In a water imbibition experiment, seed weights increased by &gt, 101.9% of their initial masses over 12 h. Effects of incubation temperature (5, 15, 20, 25, 15/6, or 25/15 °C), cold stratification period (5 °C, 0, 4, 8, or 12 weeks), and gibberellic acid (GA3, 0, 10, 100, or 1000 mg∙L−1) and potassium nitrate treatment (KNO3, 0, 1000, 2000, or 4000 mg∙L−1) on seed germination were investigated to characterize seed dormancy. These seeds exhibited underdeveloped embryos during seed dispersal. The seeds failed to reach the final germination of 15.0% after treatment at 5, 15, 20, 25, 15/6, or 25/15 °C. After cold stratification for 8 weeks, the germination increased dramatically by &gt, 90.0% compared to that at 0 weeks. After the GA3 treatment, the germination reached &gt, 80.0% within 5 days. The final germination was 90.0% in the 100 mg∙L−1 GA3 treatment group. However, the KNO3 treatment had no effect on seed germination. Therefore, the G. triflora var. japonica seeds exhibited non-deep simple morphophysiological dormancy.

Background : Autophagy is a highly balanced process in which lysosomes remove aged and damaged organelles and cellular proteins. Autophagy is essential to maintain homeostasis in the kidneys. Methods : Using human renal tubule cells HK-2, we assessed the impact of high glucose (HG) on autophagy. We also evaluated the capability of sulforaphane (SFN) to protect the HK-2 cells from HG-induced apoptosis by modulating autophagy. Results : SFN modulated autophagy and decreased apoptosis in the HK-2 cells that were cultured in 250 mM glucose medium for two days. The reactive oxygen species (ROS) levels increased, as expected, in the cells cultured in the 250 mM glucose medium. However, the SFN decreased the ROS levels in the HK-2 cells. The overexpression of heme oxygenase-1 (HO-1) by SFN decreased the expression of LC3 and beclin-1. LC3 and beclin-1 were involved in the downregulation of caspase-3 that was observed in the HG-induced cells. Conclusion : The activation of nuclear factor E2-related factor 2 (Nrf2)-HO-1 inhibited ROS expression and subsequently attenuated autophagy and cell apoptosis after HG injury was decreased. HG injury led to the activation of autophagy and HO-1 in order to combat oxidative stress and protect against cell apoptosis. Therefore, HO-1 activation can prevent ROS development and oxidative stress during HG injury, which considerably decreases autophagy and apoptosis.

Background. Epithelial-to-mesenchymal transition (EMT) is thought to play a significant role in the advancement to chronic kidney disease and contributes to the deposition of extracellular matrix proteins and renal fibrosis relating to diabetic nephropathy. Method. We studied the effect of Nrf2-HO-1 signaling on high-glucose- (HG-) induced EMT in normal human tubular epithelial cells, that is, HK2 cells. In short, we treated HK2 cells with HG and sulforaphane (SFN) as an Nrf2 activator. EMT was evaluated by the expression activity of the epithelial marker E-cadherin and mesenchymal markers such as vimentin and fibronectin. Results. Exposure of HK2 cells to HG (60 mM) activated the expression of vimentin and fibronectin but decreased E-cadherin. Treatment of HK2 cells with SFN caused HG-induced attenuation in EMT markers with activated Nrf2-HO-1. We found that SFN decreased HG-induced production of reactive oxygen species (ROS), phosphorylation of PI3K/Akt at serine 473, and inhibitory phosphorylation of serine/threonine kinase glycogen synthase kinase-3β (GSK-3β) at serine 9. Subsequently, these signaling led to the downregulation of the Snail-1 transcriptional factor and the recovery of E-cadherin. Conclusion. The present study suggests that Nrf2-HO-1 signaling has an inhibitory role in the regulation of EMT through the modulation of ROS-mediated PI3K/Akt/GSK-3β activity, highlighting Nrf2-HO-1 and GSK-3β as potential therapeutic targets in diabetic nephropathy.

Peroxiredoxin II (Prx II), an antioxidant enzyme in the Prx family, reduces oxidative stress by decreasing the intracellular ROS levels. Osteoblast differentiation is promoted by bone morphogenetic protein 2 (BMP2), which upregulates the expression of osteoblast differentiation marker genes, through Smad1/5/9 phosphorylation. We found that Prx II expression was increased by a high dose of lipopolysaccharide (LPS) but was not increased by a low dose of LPS. Prx II itself caused a decrease in the osteogenic gene expression, alkaline phosphatase (ALP) activity, and Smad1/5/9 phosphorylation induced by BMP2. In addition, BMP2-induced osteogenic gene expression and ALP activity were higher in Prx II knockout (KO) cells than they were in wild-type (WT) cells. These inhibitory effects were mediated by protein phosphatase 2A Cα (PP2A Cα), which was increased and is known to induce the dephosphorylation of Smad1/5/9. The overexpression of Prx II increased the expression of PP2A Cα, and PP2A Cα was not expressed in Prx II KO cells. Moreover, PP2A Cα reduced the level of BMP2-induced osteogenic gene expression and Smad1/5/9 phosphorylation. LPS inhibited BMP2-induced Smad1/5/9 phosphorylation and the suppressed phosphorylation was restored by the PP2A inhibitor okadaic acid (OA). Bone phenotype analyses using microcomputed tomography (μCT) revealed that the Prx II KO mice had higher levels of bone mass than the levels of the WT mice. We hypothesize that Prx II has a negative role in osteoblast differentiation through the PP2A-dependent dephosphorylation of Smad1/5/9., Bone health: Enzyme protects against damage during stress An antioxidant enzyme actively works to reduce bone synthesis under oxidative stress conditions in order to protect bone cells from damage and cell death. Bone is generated by cells called osteoblasts, which differentiate from stem cells. In osteoporosis and diabetes, excessive reactive oxygen species (ROS) within cells can disrupt osteoblast differentiation. South Korean researchers led by Eun-jung Kim at Kyungpook National University, Daegu, and Won-Gu Jang at Daegu University, Gyeongbuk, have shown that an antioxidant enzyme, peroxiredoxin II (PrxII), helps regulate bone formation under oxidative stress. The team generated PrxII-deficient mice and compared them with healthy normal mice. Under oxidative stress conditions, the mice had higher bone mass and higher expression of genes related to bone formation than the normal mice. PrxII limits osteoblast differentiation during elevated ROS by influencing associated protein activity and signalling pathways.

The consumption of oats (Avena sativa L.) with high nutritional utility is accelerating due to the increased consumers’ demand for functional foods. In Korea, naked oats are used as food, while covered oats are used for animal feed. However, it is difficult to distinguish naked oats from covered oats when the husk is removed from the grains by a special process. The present study was carried out to investigate experimental methods that would be beneficial in the segregation of different types of oats after husk removal. Grain quality-related biochemical compounds were analyzed in a bid to differentiate the oat dehulling characteristics. In addition, 61 SSR markers were examined for genetic relationship and variety identification of oats using five naked and seven covered oat varieties. Results showed that, the contents of protein, lipid, and β-glucan were not significantly different among the oat varieties and this could not be used as an index for distinguishing oats husk character. However, in the fatty acid composition ratio,, naked oats had a higher ratio of stearic acid (C18:0) and oleic acid (C18:1) than covered oats, and covered oats had a higher ratio of linoleic acid (C18:2) and linoleic acid (C18:3) than naked oats. The assessment of SSR marker genotype revealed that 33 polymorphic bands among 12 oat varieties and 1 variety could be distinguished through the combination of polymorphic markers thus indicating the usability of these markers for variety identification in oats.

Aims CREB (cAMP response element-binding protein)-regulated transcription coactivator (CRTC2) has been reported to act as a coactivator of CREB during gluconeogenesis. The role of CRTC2 in osteoblastic differentiation has not yet been elucidated. The aim of this study is to identify the mechanism of CRTC2 in osteoblast differentiation. Main methods The mRNA expression was determined by RT-PCR and qPCR. Protein levels were measured using Western blot assay. Alkaline phosphatase (ALP) staining was performed to evaluate ALP activity. Alizarin red S (ARS) staining was performed to measure extracellular mineralization. Transcriptional activity was detected using a luciferase assay. Key findings In the present study, TNF-α was found to stimulate CRTC2 expression. However, TNF-α did not increase the gene expression of osteoblast differentiation markers and inhibited BMP2-induced osteoblastic differentiation. Overexpression of CRTC2 decreased the expression of osteogenic genes, ALP activity and extracellular matrix mineralization. Knockdown of CRTC2 restored BMP2-induced osteogenic gene expression and ALP activity. CRTC2 increased Smurf1 mRNA expression, Smurf 1 promoter activity, and protein level. Furthermore, Smurf 1 decreased Smad 1/5/9 protein levels. These results suggest that CRTC2 decreased BMP2-induced osteoblastic differentiation via Smurf 1 expression. Significance Our results indicate that CRTC2 regulates the expression of Smurf1 in osteoblast differentiation.

Chrysophanol (Chrysophanic acid; CA) is a natural anthraquinone found in Senna tora and rhubarb that has various characteristic features, including the ability to suppress adipogenesis. However, its effects on osteoblast differentiation have not been investigated. Herein, this study aimed to demonstrate the mechanism by which CA induces the osteoblast differentiation. CA increased the expression of osteogenic genes. The staining levels Alkaline phosphatase (ALP) and Alizarin Red S (ARS) were increased by chrysophanol. CA induced osteoblast differentiation through AMP-activated protein kinase (AMPK)/Small mothers against decapentaplegic (Smad1/5/9) activation in MC3T3-E1 cells. In addition, compound C, AMPK inhibitor (Comp. C)-induced cells suppressed osteogenic genes expression and AMPK/Smad1/5/9 activation. Interestingly, AMPK in the CA-induced AMPK/Smad1/5/9 signalling pathway was an upstream regulator of Smad1/5/9. In order to further dissect in bone development, we used a zebrafish model to investigate the effect of CA on bone development. These results suggest that CA stimulated bone development via AMPK/Smad1/5/9. Overall, our results demonstrate that CA promotes osteoblast differentiation via AMPK/Smad1/5/9 expression in vitro and in vivo.

To develop a radioactive metal complex platform for tumor theranostics, we introduced three radiopharmaceutical derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid-benzothiazole aniline (DO3A-BTA, L1) labeled with medical radioisotopes for diagnosis (68Ga/64Cu) and therapy (177Lu). The tumor-targeting ability of these complexes was demonstrated in a cellular uptake experiment, in which 177Lu-L1 exhibited markedly higher uptake in HeLa cells than the 177Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex. According to in vivo positron emission tomography imaging, high accumulation of 68Ga-L1 and 64Cu-L1 was clearly visualized in the tumor site, while 177Lu-L1 showed therapeutic efficacy in therapy experiments. Consequently, this molecular platform represents a useful approach in nuclear medicine toward tumor-theranostic radiopharmaceuticals when 68Ga-L1 or 64Cu-L1 is used for diagnosis, 177Lu-L1 is used for therapy, or two of the compounds are used in conjunction with each other.

To get highly efficient quasi-solid-state dye-sensitized solar cells (QSS-DSSCs) with long-term stability using polymer gel electrolytes (PGEs), well-defined ABA triblock copolymers ([Poly(methyl methacrylate)]2-block-poly(ethylene glycol)) with different end functionality and components of I-/I3- liquid electrolytes (LEs) are studied and optimized for the fabrication of PGE-based QSS-DSSCs. Triblock copolymers are synthesized in a one-step reaction using bifunctional PEG-macro chain transfer agent (MCTA) by reversible addition-fragmentation chain transfer (RAFT) polymerization. Due to the high reactivity and toxicity of sulfur-containing trithiocarbonate end groups, ABA triblock copolymers prepared from RAFT polymerization are further modified to sulfur-free 2-methylpropionitrile and 4-cyanopentanoic acid end functional triblock copolymers by radical-induced exchange reactions. Dodecyl trithiocarbonate end functional PEG-MCTA and triblock copolymers absorb UV-light in the region of 260–380 nm, whereas sulfur-free carboxylic acid and 2-methylpropionitrile end functional polymers do not absorb in that UV-light region. Among three different end functional polymers, the carboxylic acid end functional triblock copolymer has the highest thermal stability. Based on electrochemical parameters, photovoltaic performance, and long-term stability, 1,2-dimethyl-3-propylimidazolium iodide (DMPII) ionic liquid and 4-tert-butylpyridine (TBP) additive containing acetonitrile-based I-/I3- LEs are effective for PGEs. The highest power conversion efficiency (PCE) for QSS-DSSCs achieved under simulated 1-sun illumination is up to 10.34%, which is comparable with the highest PCE of 10.39% for LE-DSSCs. Considering the high reactivity, thermal stability, UV-absorption, and the toxicity of the trithiocarbonate end group, the SGT-643-C triblock copolymer with carboxylic acid end group can be a promising candidate as a sulfur-free polymeric matrix for gel electrolytes of QSS-DSSCs.

To evaluate the efficacy of 18F-FC119S as a positron emission tomography (PET) radiopharmaceutical for the imaging of Alzheimer’s disease (AD), we studied the drug absorption characteristics and distribution of 18F-FC119S in normal mice. In addition, we evaluated the specificity of 18F-FC119S for β-amyloid (Aβ) in the AD group of an APP/PS1 mouse model and compared it with that in the wild-type (WT) group. The behavior of 18F-FC119S in the normal mice was characteristic of rapid brain uptake and washout patterns. In most organs, including the brain, 18F-FC119S reached its maximum concentration within 1 min and was excreted via the intestine. Brain PET imaging of 18F-FC119S showed highly specific binding of the molecule to Aβ in the cortex and hippocampus. The brain uptake and binding values for the AD group were higher than those for the WT group. These results indicated that 18F-FC119S would be a candidate PET imaging agent for targeting Aβ plaque.

Vitexin (apigenin-8-C-d-glucopyranoside) is a flavonoid isolated from natural sources. It has been employed as an anti-oxidant, anti-inflammatory, and anti-cancer agent, and is used as a traditional Chinese medicine to treat a variety of illnesses. The present study investigated the effect of vitexin on osteoblast differentiation of C3H10T1/2 mesenchymal stem cells, MC3T3-E1 preosteoblast, mouse calvarial primary cells, and primary bone marrow stem cells (BMSCs). RT-PCR and quantitative PCR demonstrated that vitexin increased mRNA expression of the osteogenic genes distal-less homeobox 5 (Dlx5) and Runxt-related transcription factor 2 (Runx2). Vitexin also increased the Dlx5 and Runx2 protein levels, Smad1/5/9 phosphorylation, and alkaline phosphatase (ALP) activity. In addition, vitexin increased Runx2-luciferase activity. Moreover, knockdown of Runx2 attenuated the increase in ALP activity induced by vitexin. These results demonstrate that vitexin enhances osteoblast differentiation via Runx2.

Among the metal–oxide nanoparticles, pure and doped zinc oxide (ZnO) has been widely studied due to their potential applications, such as electrical, thermal and optical materials. In this context, samples of undoped ZnO and Cr-doped ZnO powders were prepared using a solution-combustion route. The formation of the combustion products was confirmed by X-ray diffraction analysis. The samples were well characterized using the Fourier transform infrared spectroscopy and scanning electron microscopy techniques. In the sample, photoluminescence studies showed that ZnO could be excited at 267 nm, while an ultraviolet emission centred at $${\sim }383\,\hbox {nm}$$ was exhibited. Antibacterial-activity testing was carried out using the disc-diffusion method.

In July 2017, a medical accident occurred in South Korea, in which I-iodide solution was misadministered to the wrong patient. Although the International Commission on Radiological Protection provided internal dose coefficients for iodine for blocked thyroid, they were not reliable enough for determining the dose to the patient (whose thyroid uptake was incompletely blocked) due to a discrepancy in biokinetics. Therefore, a personalized dose assessment was performed to derive the individual-specific dose coefficients for the patient. Initially, the thyroid biokinetics of the patient were statistically clarified by fitting bioassay monitoring results and the corresponding predicted bioassay values, which were calculated repeatedly for varying iodine transfer rates in an iodine biokinetic model. After determining the transfer rate for the patient, the individual-specific dose coefficients were then calculated in accordance with latest recommendations of the International Commission on Radiological Protection. According to the individual-specific biokinetics, the 24 h thyroid uptake fraction of iodine was estimated as 0.52%. The thyroid absorbed dose of the patient was evaluated as 21.2 Gy, which differed greatly (by about 9 Gy) from the dose evaluated simply using the reference data for blocked thyroid uptake. The personalized dose assessment carried out for the patient not only reduced considerable uncertainties in the internal dose calculation, but also improved the reliability of the calculated internal dose by adopting the latest dosimetric data, including specific absorbed fraction values based on voxel phantoms. Through the dose assessment of the patient, the methodology of personalized dose assessment considering individual-specific biokinetics was developed.

To obtain an additional pharmacological agent for the diagnosis of inflammation, we investigated the medical use of (89)Zr-oxalate as a positron emission tomography (PET) probe for the in vivo imaging of inflammation and compared its efficacy to that of 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) and sodium [(18)F]fluoride. (89)Zr-oxalate exhibited observable higher uptake in a macrophage cell line than in tumor cells. The inflammatory lesions and tumors were clearly visualized by PET imaging and autoradiography using (89)Zr-oxalate. Compared to [(18)F]FDG and sodium [(18)F]fluoride, (89)Zr-oxalate demonstrated a high selectivity index to the tumor at an early time point after injection and to inflammation at a delayed time point after injection (24 h). Through histological examination, large numbers of macrophages and neutrophils were observed in the tumor lesions with the highest (89)Zr-oxalate uptake. In a rheumatoid arthritis (RA) mouse model, (89)Zr-oxalate demonstrated a high level of accumulation in inflammatory lesions. (89)Zr-oxalate is a new strategic tool for tumor imaging and inflammatory processes.

The aim of the present study is to establish a time and cost effective Na[18F]F preparation method. The process is composed of absorbing radioactive impurities with cation exchange cartridge (CM), trapping 18F-fluroide with QMA cartridges, and formulating the product. The total preparation time determined at the end of bombardment was 4 min and the radiochemical yield was 82 % (n = 29). The final formulated Na[18F]F solution satisfies the USP criteria for quality control.

For NiMn2O4 systems, the mixed valence of manganese on B-sites arises from the displacement of bivalent cations, such as Ni2+, from A-sites to B-sites which results in a corresponding proportion of Mn3+ cations on B-sites disproportionate to Mn2+ and Mn4+, and the Mn2+ cations move to the A-sites to compensate Ni2+ vacancies. With the assistance of random crystal field fluctuations and the mixed valence of manganese eventually leads to the formation of localized small polarons which accomplish a thermally activated hopping conduction between Mn3+ and Mn4+ cations on octahedral sites. In this study, we have investigated the structural and electrical properties of NixMn3-xO4 system. And, we have comprehensively measured the electrical transport mechanism, the temperature coefficient of resistance and infrared detection performance for the application of infrared radiation detectors.

Carbohydrate responsive element binding protein (ChREBP) is a major transcription factor of lipogenesis regulated by glucose status in the liver. However, the function of ChREBP in osteogenic differentiation is unclear. The present study examined the role of ChREBP in osteoblast differentiation in MC3T3-E1 preosteoblast cell line. The mRNA expression of ChREBP, protein phosphatase 2A catalytic subunit-α (PP2A Cα) and the osteogenic genes such as, DNA-binding protein inhibitor (Id1), runt-related transcription factor-2 (Runx2), and alkaline phosphatase (ALP) was measured by qPCR and RT-PCR. Runx2, ChREBP, and PP2A Cα, protein levels were evaluated by Western blotting. ALP staining experiment was carried out to evaluate ALP enzyme activity, and a luciferase reporter assay was performed to analyze Runx2 transcriptional activity. Expression of ChREBP and PP2A Cα did not change during bone morphogenetic protein-2 (BMP2)-induced osteoblast differentiation. Overexpression of ChREBP reduced the osteogenic genes (Runx2 and ALP) expression and ALP activity, while knockdown of ChREBP had the opposite effects. Overexpression of PP2A Cα increased ChREBP expression, while inhibition of PP2A Cα using okadaic acid not only inhibited the expression of ChREBP, but also restored the mRNA and protein expression of Runx2 and activity of ALP enzyme. These results demonstrate that ChREBP inhibits BMP2-induced osteoblast differentiation in a PP2A Cα- dependent manner.

Gadolinium-neutron capture therapy (Gd-NCT) is based on the nuclear capture reaction that occurs when 157Gd is irradiated with low energy thermal neutrons to primarily produce gamma photons. Herein, we investigated the effect of neutron capture therapy (NCT) using a small molecular gadolinium complex, Gd-DO3A-benzothiazole (Gd-DO3A-BTA), which could be a good candidate for use as an NCT drug due to its ability to enter the intracellular nuclei of tumor cells. Furthermore, MRI images of Gd-DO3A-BTA showed a clear signal enhancement in the tumor, and the images also played a key role in planning NCT by providing accurate information on the in vivo uptake time and duration of Gd-DO3A-BTA. We injected Gd-DO3A-BTA into MDA-MB-231 breast tumor-bearing mice and irradiated the tumors with cyclotron neutrons at the maximum accumulation time (postinjection 6 h); then, we observed the size of the growing tumor for 60 days. Gd-DO3A-BTA showed good therapeutic effects of chemo-Gd-NCT for the in vivo tumor models. Simultaneously, the Gd-DO3A-BTA groups ([Gd-DO3A-BTA(+), NCT(+)]) showed a significant reduction in tumor size (p<0.05), and the inhibitory effect on tumor growth was exhibited in the following order: [Gd-DO3A-BTA(+), NCT(+)] > [Gd-DO3A-BTA(+), NCT(−)] > [Gd-DO3A-BTA(−), NCT(+)] > [Gd-DO3A-BTA(−), NCT(−)]. On day 60, the [Gd-DO3A-BTA(+), NCT(+)] and [Gd-DO3A-BTA(−), NCT(−)] groups exhibited an approximately 4.5-fold difference in tumor size. Immunohistochemistry studies demonstrated that new combinational therapy with chemo-Gd-NCT could treat breast cancer by both the inhibition of tumor cell proliferation and induction of apoptosis-related proteins, with in vivo tumor monitoring by MRI.

The RNA-binding motif protein 3 (RBM3) belongs to a small group of proteins whose synthesis increases during hypothermia while global protein production is slowed down. Bone homeostasis is maintained by a balance between bone resorption and bone formation. Osteoblasts are key components of the bone and have an important role in bone remodeling cycle. However, hypothermia-induced RBM3 between osteoblasts remains unclear. At 32°C, expression of RBM3 and Runx2 was increased in a time-dependent manner and mineralization was also increased. RBM3 was also increased in a time-dependent manner under osteogenic conditions. Overexpression of RBM3 increased the expression of osteogenic genes such as Runx2 and OC. The osteogenic condition-induced expressions of RBM3, Runx2 and OC gene were decreased by RBM3 siRNA. Moreover, RBM3 promoted ERK and p38 phosphorylation. The inhibitor of ERK decreased the expression of Runx2 but did not affect the expression of RBM3. Taken together, these results demonstrate that RBM3 stimulates osteoblast differentiation via the ERK signaling pathway.

Kisspeptin-10 (KP-10) acts as a tumor metastasis suppressor via its receptor, G-protein-coupled receptor 54 (GPR54). The KP-10-GPR54 system plays an important role in embryonic kidney development. However, its function in osteoblast differentiation is unknown. Osteoblast differentiation is controlled by a range of hormones and cytokines, such as bone morphogenetic protein (BMPs), and multiple transcription factors, such as Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and Distal-less homeobox 5 (Dlx5). In the present study, KP-10-treatment significantly increased the expression of osteogenic genes, including mRNA and protein levels of BMP2, in C3H10T1/2 cells. Moreover, KP-10 induced BMP2-luc activity and increased phosphorylation of Smad1/5/9. In addition, NFATc4 specifically mediated KP-10-induced BMP2 gene expression. However, KP-10 treatment did not induce expression of the BMP2 and Runx2 genes in GPR54−/− cells. To examine whether KP-10 induced secretion of BMP2 to the culture medium, we used the conditioned-medium (C.M) of KP-10 treated medium on C3H10T1/2 cells. Dlx5 and Runx2 expressions were higher in GPR54−/− cells treated with C.M than in those treated with KP-10. These results demonstrate that BMP2 protein has an autocrine effect upon KP-10 treatment. Taken together, these findings suggest that KP-10/GPR54 signaling induces osteoblast differentiation via NFATc4-mediated BMP2 expression.

Purpose. 18F-FC119S is a positron emission tomography (PET) tracer for imaging β-amyloid (Aβ) plaques in Alzheimer’s disease (AD). The aim of this study is to evaluate the efficacy of 18F-FC119S in quantitating Aβ deposition in a mouse model of early amyloid deposition (5xFAD) by PET. Method. Dynamic 18F-FC119S PET images were obtained in 5xFAD (n=5) and wild-type (WT) mice (n=7). The brain PET images were spatially normalized to the M. Mirrione T2-weighted mouse brain MR template, and the volumes of interest were then automatically drawn on the cortex, hippocampus, thalamus, and cerebellum. The specific binding of 18F-FC119S to Aβ was quantified as the distribution volume ratio using Logan graphical analysis with the cerebellum as a reference tissue. The Aβ levels in the brain were also confirmed by immunohistochemical analysis. Result. For the 5xFAD group, radioactivity levels in the cortex, the hippocampus, and the thalamus were higher than those for the WT group. In these regions, specific binding was approximately 1.2-fold higher in 5xFAD mice than in WT. Immunohistochemistry supported these findings; the 5xFAD showed severe Aβ deposition in the cortex and hippocampus in contrast to the WT group. Conclusion. These results demonstrated that 18F-FC119S PET can successfully distinguish Aβ depositions in 5xFAD mice from WT.

We have investigated a dual-ended readout detector based on two silicon photo-multipliers (SiPMs) using a 30 mm long cerium-doped lutetium-yttrium oxyorthosilicate ( ${\rm Lu}_{0.5}{{\rm Y}_{1.4}}{\rm Si}_{0.5}:{\rm Ce}$ , LYSO) crystal to study the feasibility of a time-of-flight (TOF) and depth-of-interaction (DOI) positron emission tomography (PET). To improve the timing resolution in the dual-ended readout detector, a novel meantime measurement was employed. The meantime was obtained by averaging two signal arrival times at two SiPMs, each of which was attached to both ends of the LYSO crystal. The meantime method minimizes the arrival time difference along the crystal. Both timing and DOI resolutions using the meantime method were better than those of a single-ended readout detector.

In this paper to improve the ionic conduction properties, lanthanum silicate apatite ceramic, which substituted by V ions at Si-site, were fabricated by the mixed-oxide method. And we investigated the structural and electrical properties of specimens with variation of dopants for the application of solid oxide fuel cells. The sintering temperature of specimens decreased from to . As results of X-ray diffraction patterns, all specimens showed the formation of a complete solid solution in a apatite polycrystallin structure. But the specimens doped with more than 1.5mol% showed the second phase, and . The specimen dopants with 1.0 mol% showed the maximum ion conductivity. Ion conducting and activation energy of the specimens were about 1.62 eV at , respectively.

Cadmium zinc telluride (CZT)-based small-animal single-photon emission computed tomography (SPECT) has desirable characteristics such as superior energy resolution, but data acquisition for SPECT imaging has been widely performed with a conventional energy window. The aim of this study was to determine the optimal energy window settings for technetium-99 m ( 99m Tc) and thallium-201 ( 201 Tl), the most commonly used isotopes in SPECT imaging, using CZT-based small-animal SPECT for quantitative accuracy. We experimentally investigated quantitative measurements with respect to primary count rate, contrast-to-noise ratio (CNR), and scatter fraction (SF) within various energy window settings using Triumph X-SPECT. The two ways of energy window settings were considered: an on-peak window and an off-peak window. In the on-peak window setting, energy centers were set on the photopeaks. In the off-peak window setting, the ratios of energy differences between the photopeak from the lower- and higher-threshold varied from 4:6 to 3:7. In addition, the energy-window width for 99m Tc varied from 5% to 20%, and that for 201 Tl varied from 10% to 30%. The results of this study enabled us to determine the optimal energy windows for each isotope in terms of primary count rate, CNR, and SF. We selected the optimal energy window that increases the primary count rate and CNR while decreasing SF. For 99m Tc SPECT imaging, the energy window of 138–145 keV with a 5% width and off-peak ratio of 3:7 was determined to be the optimal energy window. For 201 Tl SPECT imaging, the energy window of 64–85 keV with a 30% width and off-peak ratio of 3:7 was selected as the optimal energy window. Our results demonstrated that the proper energy window should be carefully chosen based on quantitative measurements in order to take advantage of desirable characteristics of CZT-based small-animal SPECT. These results provided valuable reference information for the establishment of new protocol for CZT-based small-animal study, and may offer insights into the potential of multiple-isotope imaging with CZT-based small-animal SPECT.

Gastrin‑releasing peptide receptor (GRPR) is overexpressed by a variety of human tumors and in particular, identified to be upregulated in prostate cancers. The current study aimed to develop clinically translatable BBN analogue‑based radioligands for positron emission tomography (PET) of GRPR‑positive tumors. We developed radiolabeled BBN analogues and modified radiolabeled galacto‑BBN analogues and then investigated their tumor‑targeting efficacy in vivo. The chelator 1,4,7‑triazacyclononane, 1‑glutaric acid‑4,7 acetic acid (NODAGA) was used to radiolabel the peptides with 64Cu. The peptides were evaluated by measuring cell‑based receptor‑binding affinities. Biodistribution experiments and small animal imaging using PET were performed in nude mice bearing subcutaneous PC3 human prostate cancer xenografts. The conjugates were radiolabeled with yields >99%. The stability assay showed that [64Cu]NODAGA‑BBN and [64Cu]NODAGA‑galacto‑BBN remained stable in both human and mouse serum for 1 h at 37˚C. PET images of PC3 tumor‑bearing nude mice were acquired at 1, 3, 24, 48 and 72 h after injection. [64Cu]NODAGA‑galacto‑BBN showed retention in tumors for 72 h, low liver uptake, and rapid renal clearance. PET imaging results were also confirmed by biodistrubution 1 and 3 h after injection. [64Cu]NODAGA‑BBN and [64Cu]NODAGA‑galacto‑BBN are promising new PET probes for GRPR‑positive prostate cancer.

Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

Zaluzanin C (ZC) is a sesquiterpene lactones used in herbal medicines. This study examined the effects of ZC on osteoblast differentiation. ZC-induced mRNA expressions levels of osteogenic genes in C3H10T1/2 and MC3T3-E1 cells were determined by RT-PCR and qPCR. ZC regulated the expression of key osteogenic genes in the early stage of differentiation, including distal-less homeobox 5 (Dlx5), DNA-binding protein inhibitor (Id1) and Runt-related transcription factor 2 (Runx2). In addition, ZC increased Runx2 promoter activity, as assessed via a luciferase assay, and Runx2 protein level. These results suggest that ZC may enhance osteoblast differentiation by upregulating the expression of osteogenic genes, especially early stage like as Dlx5, Id1 and Runx2.

We investigated the effects of hypothyroidism on serotonin 1A receptors in the rat brain in vivo. Five surgically thyroidectomized male Sprague–Dawley (SD) rats and five hypophysectomized SD rats were used as animal models of hypothyroidism; the same number of sham-operated SD rats served as age-matched controls. After hypothyroidism was confirmed by thyroid function tests, serotonin positron emission tomography (PET) was performed for 120 min. All PET data were spatially normalized to T2-weighted magnetic resonance imaging templates; then, time-activity curves of the hippocampus, septum, and cerebellum were extracted using predefined volume-of-interest templates. Non-displaceable binding values in the hippocampus and septum were calculated using a multilinear reference tissue model and parametric maps were constructed. Both volume-of-interest and voxel-based analyses showed higher brain uptake in the thyroidectomized and hypophysectomized rats compared to the respective sham-operated rats. Time-activity curves showed that the brain uptake values for the thyroidectomized and hypophysectomized groups were 21–52% higher than were those in the respective control groups. In the thyroidectomized group, the binding potential values for the hippocampus and septum were 20–26% higher than were those in the sham-thyroidectomized group. In the hypophysectomized group, the binding value for the hippocampus was 23% higher than was that in the sham-hypophysectomized group, whereas the septal binding was not significantly different from that in the sham-hypophysectomized group. Parametric maps for the hypothyroidism also showed significantly higher binding values than did those for the controls. Our results demonstrate that hypothyroidism elevates serotonin 1A receptor binding in the limbic system.

Aims Costunolide is a sesquiterpene lactones used in many herbal medicines, with well-established anti-inflammatory and anti-oxidant functions modulating endoplasmic reticulum (ER) stress pathways, and which promotes the expression of anti-oxidant genes. The aim of this study is to investigate whether costunolide is involved in osteoblast differentiation and, determine the mechanisms of differentiation in mesenchymal stem cells. Main methods The cytotoxicity of costunolide was identified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The mRNA and protein expression levels of osteogenic genes were determined by RT-PCR and Western blot analysis. Alkaline phosphate (ALP) staining and Alizarin red S (ARS) staining were performed to evaluate ALP activity and matrix mineralization. Transcriptional activity was detected using a luciferase reporter assay. Key findings In this study, we determined that costunolide increased the expression of distal-less homeobox 5 (Dlx5), runt-related transcription factor 2 (Runx2), ALP, and osteocalcin (OC) in C3H10T 1/2 cells. Furthermore, costunolide increased ALP activity and matrix mineralization. Interestingly, costunolide increased ER stress by Bip, activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP). However, it did not exert effects on expression of activating transcription factor 6 (ATF6). ATF4 activation has a protective role in oxidative stress, and its transcription induces anti-oxidant genes in cells. Heme oxygenase-1 (HO-1) is a major anti-oxidant enzyme, and is regulated by ATF4. We showed that costunolide treatment increased HO-1 expression. Furthermore, the HO-1 inhibitor, Sn(IV) Protoporphyrin IX dichloride (SnPP) was blocked costunolide-induced Runx2 expression. Significance Our results revealed that costunolide-induced osteoblast differentiation is regulated by ATF4-dependent HO-1 expression.

Purpose. Radiation-induced lung fibrosis (RILF) is a serious late complication of radiotherapy. In vitro studies have demonstrated that pentoxifylline (PTX) has suppressing effects in extracellular matrix production in fibroblasts, while the antifibrotic action of PTX alone using clinical dose is yet unexplored.Materials and Methods. We used micro-computed tomography (micro-CT) and histopathological analysis to evaluate the antifibrotic effects of PTX in a rat model of RILF.Results. Micro-CT findings showed that lung density, volume loss, and mediastinal shift are significantly increased at 16 weeks after irradiation. Simultaneously, histological analysis demonstrated thickening of alveolar walls, destruction of alveolar structures, and excessive collagen deposition in the irradiated lung. PTX treatment effectively attenuated the fibrotic changes based on both micro-CT and histopathological analyses. Western analysis also revealed increased levels of plasminogen activator inhibitor- (PAI-) 1 and fibronectin (FN) and PTX treatment reduced expression of PAI-1 and FN by restoring protein kinase A (PKA) phosphorylation but not TGF-β/Smad in both irradiated lung tissues and epithelial cells.Conclusions. Our results demonstrate the antifibrotic effect of PTX on radiation-induced lung fibrosis and its effect on modulation of PKA and PAI-1 expression as possible antifibrotic mechanisms.

The thymidine analogue 3′-deoxy-3′-[18F]fluorothymidine, or [18F]fluorothymidine ([18F]FLT), is used to measure tumor cell proliferation with positron emission tomography (PET) imaging technology in nuclear medicine. FLT is phosphorylated by thymidine kinase 1 (TK1) and then trapped inside cells; it is not incorporated into DNA. Imaging with18F-radiolabeled FLT is a noninvasive technique to visualize cellular proliferation in tumors. However, it is difficult to distinguish between [18F]FLT and its metabolites by PET imaging, and quantification has not been attempted using current imaging methods. In this study, we successfully acquiredin vivoF19spectra of natural or nonradioactive 3′-deoxy-3′-fluorothymidine ([19F]FLT) and its monophosphate metabolite (FLT-MP) in a tumor xenograft mouse model using 9.4T magnetic resonance imaging (MRI). This preliminary result demonstrates that19F magnetic resonance spectroscopy (MRS) with FLT is suitable for thein vivoassessment of tumor aggressiveness and for early prediction of treatment response.

Two new bicyclic arginine-glycine-aspartic acid (RGD) peptides, c(RGD-ACP-K) (1a) and c(RGD-ACH-K) (1b), incorporating the aminocyclopentane (ACP) and aminocyclohexane (ACH) carboxylic acids, respectively, were synthesized by grafting the aminocycloalkane carboxylic acids onto the tetra-peptide RGDK sequence. These peptides and their conjugates with DO3A (1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid) (2a-b) exhibit high affinity toward U87MG glioblastoma cells. Their affinity is greater than that exhibited by c(RGDyK). Labeling these conjugates with radiometal (64)Cu resulted in high radiochemical yields (97%) of the corresponding complexes, abbreviated as c(RGD-ACP-K)-DOTA-(64)Cu (3a) and c(RGD-ACH-K)-DOTA-(64)Cu (3b). Both 3a and 3b are stable for 24 h in human and mouse serums and show high tumor uptake, as observed by positron emission tomography (PET). Blocking experiments with 3a and 3b by preinjection of c(RGDyK) confirmed their target specificity and demonstrated their promise as PET radiotracers for imaging ανβ3-positive tumors.

Purpose The aim of this study is to integrate NIR, gamma, and visible imaging tools into a single endoscopic system to overcome the limitation of NIR by using gamma imaging and to demonstrate the feasibility of endoscopic NIR/gamma/visible fusion imaging for sentinel lymph node (SLN) mapping with a small animal. Methods The endoscopic NIR/gamma/visible imaging system consists of a tungsten pinhole collimator, a plastic focusing lens, a BGO crystal (11 × 11 × 2 mm3), a fiber optic taper (front = 11 × 11 mm2, end = 4 × 4 mm2), a 122 cm long endoscopic fiber bundle, an NIR emission filter, a relay lens, and a CCD camera. A custom-made Derenzo-like phantom filled with a mixture of 99mTc and indocyanine green (ICG) was used to assess the spatial resolution of the NIR and gamma images. The ICG fluorophore was excited using a light-emitting diode (LED) with an excitation filter (723-758 nm), and the emitted fluorescence photons were detected with an emission filter (780-820 nm) for a duration of 100 ms. Subsequently, the 99mTc distribution in the phantom was imaged for 3 min. The feasibility of in vivo SLN mapping with a mouse was investigated by injecting a mixture of 99mTc-antimony sulfur colloid (12 MBq) and ICG (0.1 mL) into the right paw of the mouse (C57/B6) subcutaneously. After one hour, NIR, gamma, and visible images were acquired sequentially. Subsequently, the dissected SLN was imaged in the same way as the in vivo SLN mapping. Results The NIR, gamma, and visible images of the Derenzo-like phantom can be obtained with the proposed endoscopic imaging system. The NIR/gamma/visible fusion image of the SLN showed a good correlation among the NIR, gamma, and visible images both for the in vivo and ex vivo imaging. Conclusion We demonstrated the feasibility of the integrated NIR/gamma/visible imaging system using a single endoscopic fiber bundle. In future, we plan to investigate miniaturization of the endoscope head and simultaneous NIR/gamma/visible imaging with dichroic mirrors and three CCD cameras. This article is protected by copyright. All rights reserved.

Purpose : Multimodality imaging contributes to the activation of translational research by compensating for its weak points. Herein, we developed a noninvasive dual-reporter gene system for nuclear and optical imaging. Materials and methods : We constructed a fusion reporter vector concurrently expressing the human sodium/iodide symporter (hNIS) and monomeric red fl uorescent protein (mCherry), and evaluated the function of this fusion reporter system under in vitro and in vivo conditions. Results : The expression of hNIS/mCherry fusion gene was confi rmed in transfected cells using reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. As the numbers of cells increased, the fl uorescence and 125 I uptake increased in the hNIS/mCherry-transfected cells, and a high correlation between fl uorescence intensity and radioactivity was noted. The fl uorescence intensities and radioactivity signals were also well-correlated in HT-29-hNIS/mCherry tumors (R 2 0.9304) in in vivo fl uorescence and gamma camera imaging. Conclusions : The dual-reporter imaging method using hNIS and mCherry genes refl ected tumor extent as well as viable cell numbers, and correlated well with one another. This suggests that the hNIS/mCherry dual-reporter system can be a useful tool for multi-modal imaging.

The goal of this investigation was to evaluate the effects of structural differences between FIAU and FIRU on their ability to serve as a potential tracer for reporter gene imaging. To examine the characteristics of different configurations of FIAU and FIRU, a series of evaluations were done on HSV1-TK gene-expressing cells and on mice with HSV1-TK gene-expressing tumor. The results showed that, as an imaging agent for HSV1-TK-expressing cells, radiolabeled FIAU was more efficient for in vivo imaging than FIRU.

A p-type ZnO thin film was prepared using arsenic diffusion via the ampoule-tube method. This was followed by fabrication of a ZnO p–n homojunction using n-type ZnO and characterization of the device properties. The ZnO thin film exhibited p-type characteristics, with a resistivity of 2.19×10−3 Ω cm, a carrier concentration of 1.73×1020/cm3, and a mobility of 26.7 cm2/V s. Secondary ion mass spectrometer analysis confirmed that in- and out-diffusion occurred simultaneously from the external As source and the GaAs substrate. The device exhibited the rectification characteristics of a typical p–n junction; the forward voltage at 20 mA was approximately 5.5 V. The reverse-bias leakage current was very low—0.1 mA for −10 V; the breakdown voltage was −11 V. The ampoule-tube method for fabricating p-type ZnO thin films may be useful in producing ultraviolet ZnO LEDs and other ZnO-based devices.

201Tl has been extensively used for myocardial perfusion and viability assessment. Unlike 99mTc-labelled agents, such as 99mTc-sestamibi and 99mTc-tetrofosmine, the regional concentration of 201Tl varies with time. This study is intended to validate a kinetic modelling approach for in vivo quantitative estimation of regional myocardial blood flow (MBF) and volume of distribution of 201Tl using dynamic SPECT.Dynamic SPECT was carried out on 20 normal canines after the intravenous administration of 201Tl using a commercial SPECT system. Seven animals were studied at rest, nine during adenosine infusion, and four after beta-blocker administration. Quantitative images were reconstructed with a previously validated technique, employing OS-EM with attenuation-correction, and transmission-dependent convolution subtraction scatter correction. Measured regional time-activity curves in myocardial segments were fitted to two- and three-compartment models. Regional MBF was defined as the influx rate constant (K(1)) with corrections for the partial volume effect, haematocrit and limited first-pass extraction fraction, and was compared with that determined from radio-labelled microspheres experiments.Regional time-activity curves responded well to pharmacological stress. Quantitative MBF values were higher with adenosine and decreased after beta-blocker compared to a resting condition. MBFs obtained with SPECT (MBF(SPECT)) correlated well with the MBF values obtained by the radio-labelled microspheres (MBF(MS)) (MBF(SPECT) = -0.067 + 1.042 x MBF(MS), p0.001). The three-compartment model provided better fit than the two-compartment model, but the difference in MBF values between the two methods was small and could be accounted for with a simple linear regression.Absolute quantitation of regional MBF, for a wide physiological flow range, appears to be feasible using 201Tl and dynamic SPECT.

Introduction The purpose of this research is to evaluate the prospects for the use of 4-(trans-18F-fluoranylmethyl)-N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexane-1-carboxamide (18F-Mefway) in comparison to 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (18F-FCWAY) for the quantification of 5-HT1A receptors in human subjects. Method Five healthy male controls were included for two positron emission tomography (PET) studies: 18F-FCWAY PET after the pretreatment with 500 mg of disulfiram and two months later, 18F-Mefway PET without disulfiram. Regional time-activity curves (TACs) were extracted from nine cortical and subcortical regions in dynamic PET images. Using cerebellar cortex without vermis as reference tissue, in vivo kinetics for both radioligands were compared based on the distribution volume ratio (DVR) calculated by non-invasive Logan graphical analysis and area under the curve ratio of the TACs (AUC ratio). Result Although the pattern of regional uptakes in the 18F-Mefway PET was similar to that of the 18F-FCWAY PET (highest in the hippocampus and lowest in the cerebellar cortex), the amount of regional uptake in 18F-Mefway PET was almost half of that in 18F-FCWAY PET. The skull uptake in 18F-Mefway PET was only 25% of that in 18F-FCWAY PET with disulfiram pretreatment. The regional DVR values and AUC ratio values for 18F-Mefway were 17—40% lower than those of 18F-FCWAY. In contrast to a small overestimation of DVR values by AUC ratio values (< 10%) in 18F-FCWAY PET, the overestimation bias of AUC ratio values was much higher (up to 21%) in 18F-Mefway PET. Conclusion As 18F-Mefway showed lower DVR values and greater overestimation bias of AUC ratio values, 18F-Mefway may appear less favorable than 18F-FCWAY. However, in contrast to 18F-FCWAY, the resistance to in vivo defluorination of 18F-Mefway obviates the need for the use of a defluorination inhibitor. Thus, 18F-Mefway may be a good candidate PET radioligand for 5-HT1A receptor imaging in human.

The coupling of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2) during physiological and pathological conditions remains a subject of debate. We have developed a physiological model for oxygen delivery and metabolism, which allows the estimation of net oxygen diffusibility at the capillary level, termed “effective oxygen diffusibility (EOD).” The results of PET in monkeys showed dynamic changes in EOD in response to changes in oxygen delivery and consumption. EOD is defined as capillary volume and permeability product, but its change mainly reflects the pericapillary oxygen gradient as long as capillary architecture is preserved. EOD may have sufficient predictability to represent the tissue oxygen demand and application of the model to PET data. In the future, EOD may give us further insight to understand the physiological regulatory system for oxygen demand in the brain.

Prior studies with anthropomorphic phantoms and single, static in vivo brain images have demonstrated that scatter correction significantly improves the accuracy of regional quantitation of single-photon emission tomography (SPET) brain images. Since the regional distribution of activity changes following a bolus injection of a typical neuroreceptor ligand, we examined the effect of scatter correction on the compartmental modeling of serial dynamic images of striatal and extrastriatal dopamine D(2) receptors using [(123)I]epidepride. Eight healthy human subjects [age 30+/-8 (range 22-46) years] participated in a study with a bolus injection of 373+/-12 (354-389) MBq [(123)I]epidepride and data acquisition over a period of 14 h. A transmission scan was obtained in each study for attenuation and scatter correction. Distribution volumes were calculated by means of compartmental nonlinear least-squares analysis using metabolite-corrected arterial input function and brain data processed with scatter correction using narrow-beam geometry micro (SC) and without scatter correction using broad-beam micro (NoSC). Effects of SC were markedly different among brain regions. SC increased activities in the putamen and thalamus after 1-1.5 h while it decreased activity during the entire experiment in the temporal cortex and cerebellum. Compared with NoSC, SC significantly increased specific distribution volume in the putamen (58%, P=0.0001) and thalamus (23%, P=0.0297). Compared with NoSC, SC made regional distribution of the specific distribution volume closer to that of [(18)F]fallypride. It is concluded that SC is required for accurate quantification of distribution volumes of receptor ligands in SPET studies.