• Nuclear Medicine and Molecular Imaging
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• v.42 no.sup1
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• pp.177-180
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• 2008

Parkinson's disease is the second most common neurodegenerative disorder. It is slowly progressive disease that affects a small area of cells in the mid brain known as the substantia nigra. Gradual degeneration of these cells causes a reduction in a vital chemical known as dopamine. In the diagnosis of Parkinson's disease, it has difficulty in biopsy and limits in radiologic modalities. $^{18}F-FDG$ PET shows various findings from normal to diffuse decrement of FDG uptake. $^{18}F-FDG$ PET is expected to be a evaluation tool in the treatment of Parkinson's disease.

• The Korean Journal of Nuclear Medicine
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• v.29 no.3
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• pp.328-331
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• 1995

$^{99m}Tc$ labeled PnAO(propylene amine oxime) derivatives have been widely studied as brain perfusion agents. We synthesized and characterized a PnAO derivative, (RR/SS/ meso)-4,8-diaza-3,9-dimethylundecane-2, 10-dione bisoxime(PRODD). Proton-NMR spectroscopy and thin layer chromatography(silica gel) were performed for its characterization. PRODD was labeled with $^{99m}Tc$ using stannous chloride as reducing agent. The labeling efficiency was determined to be about 85%. Brain uptakes of $4.16{\pm}0.42$ %ID/g and $3.24{\pm}0.13$ %ID/g were found after 10min and 30min after intravenous injection. Brain-to-blood ratios were 1.17 and 0.75 at 10 and 30 minutes, which were lower than 1.3 and 1.9 of the ratios with commercial ${\pm}$-HMPAO. Autoradiographs of rat brain sections showed the gray matter to white matter ratios of $1.13{\pm}0.10$ at 30 min after intravenous injection, which was lower than $1.94{\pm}0.19$ of commercial $^{99m}Tc$-HMPAO. With the above findings, we concluded that the lipophilic $^{99m}Tc$-PRODD complex was able to cross the blood-brain barrier, however the complex showed lower uptake than $^{99m}Tc$-HMPAO in mouse or rat brains. We could suggest possibility that PRODD could be used as another $^{99m}Tc$ chelator.

• The Korean Journal of Nuclear Medicine
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• v.38 no.3
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• pp.241-252
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• 2004

Purpose: Population based structural and functional maps of the brain provide effective tools for the analysis and interpretation of complex and individually variable brain data. Brain MRI and PET standard templates and statistical probabilistic maps based on image data of Korean normal volunteers have been developed and probabilistic maps based on cytoarchitectonic data have been introduced. A quantification method using these data was developed for the objective assessment of regional intensity in the brain images. Materials and Methods: Age, gender and ethnic specific anatomical and functional brain templates based on MR and PET images of Korean normal volunteers were developed. Korean structural probabilistic maps for 89 brain regions and cytoarchitectonic probabilistic maps for 13 Brodmann areas were transformed onto the standard templates. Brain FDG PET and SPGR MR images of normal volunteers were spatially normalized onto the template of each modality and gender. Regional uptake of radiotracers in PET and gray matter concentration in MR images were then quantified by averaging (or summing) regional intensities weighted using the probabilistic maps of brain regions. Regionally specific effects of aging on glucose metabolism in cingulate cortex were also examined. Results: Quantification program could generate quantification results for single spatially normalized images per 20 seconds. Glucose metabolism change in cingulate gyrus was regionally specific: ratios of glucose metabolism in the rostral anterior cingulate vs. posterior cingulate and the caudal anterior cingulate vs. posterior cingulate were significantly decreased as the age increased. 'Rostral anterior'/'posterior' was decreased by 3.1% per decade of age ($P<10^{-11}$, r=0.81) and 'caudal anterior'/'posterior' was decreased by 1.7% ($P<10^{-8}$, r=0.72). Conclusion: Ethnic specific standard templates and probabilistic maps and quantification program developed in this study will be useful for the analysis of brain image of Korean people since the difference in shape of the hemispheres and the sulcal pattern of brain relative to age, gender, races, and diseases cannot be fully overcome by the nonlinear spatial normalization techniques.

• The Korean Journal of Nuclear Medicine
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• v.38 no.4
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• pp.288-293
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• 2004

Purpose: increased uptake of wrist and hand joints in three phase bone scintigraphy (TPBS) have been used in the detection of reflex sympathetic dystrophy syndrome (RSDS). TPBS frequently shows increased shoulder uptake in the hemiplegic RSDS patients. We investigated the significance of the shoulder uptake in the detection of these patients. Materials and Methods: Twenty three patients who had hemiplegia due to brain stroke and diagnosed as RSD were enrolled in this study (M:F=16:7, R:L=11:12). The mean age was $63{\pm}10$ yrs. Ter normal volunteer (mean age: $60{\pm}5$, M:F=1:9) data was used as control group. TPBS was performed $59{\pm}32$ days after stoke (acute stage). We obtained the count ratios of bilateral hands by drawing a region of interest (ROI) in three phase images and compared to the count ratios of shoulders in the delayed image. Hand ROI included an ipsilateral wrist. Sensitivity of detecting the affected limb was defined using the right/left count ratio of normal control. Results: Sensitivities using count ratios of hand blood flow, blood pool and delayed image were 45%, 76% and 78%, respectively. Sensitivity of shoulder count ratio was 74%. Log of right/left counts of hand delayed image and that of shoulder delayed image were correlated well with statistical significance (Spearman's R=0.824, p<0.001). Conclusion: Shoulder uptake showed good correlation with hand uptake in the delayed image of TPBS. Shoulder uptake maybe helpful in the diagnosis of reflex sympathetic dystrophy syndrome in patients with hemiplegia.

• The Korean Journal of Nuclear Medicine
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• v.34 no.4
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• pp.294-302
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• 2000

Purpose: To investigate the mechanisms related to F-18-FDG uptake by tumors, F-18-FDG accumulation was compared with glucose transporter-1 (Glut-1) expression and hexokinase activity in various human cancer cell lines. Materials and Methods: Human colon cancer (SNU-C2A, SNU-C4, SNU-C5), hepatocellular carcinoma (SNU-387, SNU-423, SNU-449), lung cancer (NCI-H522, NCI-H358, NCI-H1299), uterine cervical cancer (HeLa, HeLa 229, HeLa S3) and brain tumor (A172, Hs 683) cell lines were used. After 24 hr incubation of $5{\times}10^5$ cells, 37 kBq F-18-FDG was added and the uptake by cells at 10 min was measured using a gamma counter. Hexokinase activity was measured by continuous spectrophotometric rate determination. To measure mitochondrial hexokinase activity, mitochondrial fraction was separated by a high speed centrifuge. Immunohistochemical staining of Glut-1 was performed, and graded as 0, 1, 2, or 3 according to expression. Results: There was difference among F-18-FDG uptake, total and mitochondrial hexokinase activity, and Glut-1 expression with different cancer cell lines. The correlations of F-18-FDG with total hexokinase and mitochondrial hexokinase activity were low (r=0.27 and 0.26, respectively). Glut-1 expression showed a good correlation with F-18-FDG uptake (p=0.81, p=0.0015). Previously, we reported no correlation of F-18-FDG uptake with hexokinase activity in colon cancer cell lines. Thus, when colon cancer cells were excluded, F-18-FDG uptake showed higher correlation with total hexokinase and mitochondrial hexokinase activity (r=0.81, p=0.0027 and r=0.81, p=0.0049, respectively). Conclusion: Both Glut-1 expression and hexokinase activity were contributing factors related to F-18-FDG accumulation in human cancer cell lines. The relative contribution of Glut-1 expression and hexokinase activity, however, was different among different cancer cell types.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.5
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• pp.263-270
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• 2006

Purpose: Several radioisotope-labeled thymidine derivatives such as $[^{11}C]$thymidine was developed to demonstrate cell proliferation in tumor. But it is difficult to track metabolism with $[^{11}C]$thymidine due to rapid in vivo degradation and its short physical half-life. 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT) was reported to have the longer half life of fluorine-18 and the lack of metabolic degradation in vivo. Here, we described the synthesis of the 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT) and compared with $([^{18}F]FET)\;and\;([^{18}F]FDG)$ in cultured 9L cell and obtained the biodistribution and PET image in 9L tumor hearing rats. Material and Methods: For the synthesis of $[^{18}F]$FLT, 3-N-tert-butoxycarbonyl-(5'-O-(4,4'-dimet hoxytriphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-${\beta}$-D-threopentofuranosyl)thymine was used as a FLT precursor, on which the tert-butyloxycarbonyl group was introduced to protect N3-position and nitrobenzenesulfonyl group. Radiolabeling of nosyl substitued precursor with $^{18}F$ was performed in acetonitrile at $120^{\circ}C$ and deproteced with 0.5 N HCI. The cell uptake was measured in cultured 9L glioma cell. The biodistribution was evaluated in 9L tumor bearing rats after intravenous injection at 10 min, 30 min, 60 min and 120 min and obtained PET image 60 minutes after injection. Results: The radiochemical yield was about 20-30% and radiochemical purity was more than 95% after HPLC purification. Cellular uptake of $[^{18}F]$FLT was increased as time elapsed. At 120 min post-injection, the ratios of tumor/blood, tumor/muscle and tumor/brain were $1.61{\pm}0.34,\;1.70{\pm}0.30\;and\;9.33{\pm}2.22$, respectively. The 9L tumor was well visualized at 60 min post injection in PET image. Conclusion: The uptake of $[^{18}F]$FLT in tumor was higher than in normal brain and PET image of $[^{18}F]$FLT was acceptable. These results suggest the possibility of $[^{18}F]$FLT at an imaging agent for brain tumor.

• Molecules and Cells
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• v.23 no.1
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• pp.11-16
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• 2007

N,N-dimethyl-D-erythro-sphingosine (DMS) is an N-methyl derivative of sphingosine and an inhibitor of protein kinase C (PKC) and sphingosine kinase (SK). In the present study, we examined the effects of DMS on intracellular $Ca^{2+}$ concentration, pH, and glutamate uptake in human 1321N1 astrocytes. DMS increased intracellular $Ca^{2+}$ concentration and cytosolic pH in a concentration-dependent manner. Pretreatment of the cells with the $G_{i/o}$ protein inhibitor PTX and the PLC inhibitor U73122 had no obvious effect. However, removal of extracellular $Ca^{2+}$ with the $Ca^{2+}$ chelator EGTA or depletion of intracellular $Ca^{2+}$ stores with thapsigargin impeded the DMS-induced increase of intracellular $Ca^{2+}$ concentration. Pretreatment of cells with $NH_4Cl$ or monensin reduced the DMS-induced $Ca^{2+}$ increase. However, inhibition of the DMS-induced $Ca^{2+}$ increase with BAPTA did not influence the DMS-induced pH increase. DMS also inhibited glutamate uptake by the 1321N1 astrocytes in a concentration-dependent manner. It also increased intracellular $Ca^{2+}$ and pH in PC12 neuronal cells. Our observations on the effects of DMS on 1321N1 astrocytes and PC12 neuronal cells point to a physiological role of DMS in the brain.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.5
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• pp.791-796
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• 2004

This study was peformed to screen the biological activities of Pleurotus ferulea (K5 and K8 strains). The cap of K5 strain is well developed than stalk, and vice versa in K8. The ethanol extract of Pleurotus ferulea exhibited significant free radical scavenging activity (35∼36%), suggesting possible effect on many degenerative diseases originated from the reaction of oxygen species. Acetylcholinesterase inhibitor is proven to be the most effective factor for Alzheimer disease induction, and ethanol extract of Pleurotus ferulea significantly inhibited acetylcholinesterase activity (25∼35%) in uitro. Moreover, ethanol extract of Pleurotus ferulea suppressed liver fibrosis by 3∼12% in uitro. However, Pleurotus ferulea feruled to inhibit glucose uptake in human intestinal cell line. Viability of gastric and colon cancer cells was also not affected by Pleurotus ferulea extract. In conclusion Pleurotus ferulea exhibited significant effect on free radical scavenging, acetylcholinesterase inhibiton and brain cell protection. However, Pleurotus ferulea failed to affect glucose uptake, and cytotoxicity of gastric and cancer cells. In general, K8 revealed more significant effects than K5.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.10
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• pp.1626-1633
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• 2004

In recent, the roles of oleic acid, most abundant fatty acid in myelin, were investigated in relation to the brain functions. This study examined the effects of diets either with desirable ratios of $\omega$6/ $\omega$9 and P/M/S (mixed oil-fed group: MO) or with defficient in $\omega$3 series fatty acids (safflower oil-fed group: SO) on the oleic acid composition in RBC and brain synaptosomal, mitochondrial & microsomal phospholipids. The desirable fatty acid composition was computer-searched with different fats and oils to meet right ratios of both $\omega$6/ $\omega$3 and P/M/S. Diets were fed 3 weeks before conception and new-born pups were fed maternal milk from the same mothers and same diets until 9 wks of age. At 3 wks of age, the compositions of oleic acid in brain subcellular fractions and red blood cells were constantly remained whatever the composition of dietary fatty acids. But at 9 wks of age, the composition of oleic acid in synaptosome and mitochondria were significantly higher in MO group than SO group. The composition of oleic acid in milk was significantly higher in MO group than SO group, but in case of SO group, that of oleic acid was increased by 48%, in comparison with dietary fatty acid compositions. -9 desaturase index (18:0\longrightarrow8:1) of brain synaptosome was significantly higher in MO group than SO group at 3 and 9 weeks of ages, but that of brain microsome was higher in SO group than MO group at 9 wks of age. Taken together, the presences of oleic acid in the diet was important to maintain brain functions. The origins of oleic acid in brain may suggests two hypotheses; first, the central nervous system has priority for the uptake of oleic acid, and second the nervous system can synthesize all the oleic acid it needs, independently of its presence in the diet.

• Journal of Korean Neurosurgical Society
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• v.56 no.5
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• pp.383-389
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• 2014

Objective : Neural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons. In this present study, aggregates of human brain-derived neural stem cells (HB-NSC) were transplanted into a PD animal model and compared to previous report on transplantation of single-cell suspensions. Methods : Rats received an injection of 6-OHDA into the right medial forebrain bundle to generate the PD model and followed by injections of PBS only, or HB-NSC aggregates in PBS into the ipsilateral striatum. Behavioral tests, multitracer (2-deoxy-2-[$^{18}F$]-fluoro-D-glucose ([$^{18}F$]-FDG) and [$^{18}F$]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([$^{18}F$]-FP-CIT) microPET scans, as well as immunohistochemical (IHC) and immunofluorescent (IF) staining were conducted to evaluate the results. Results : The stepping test showed significant improvement of contralateral forelimb control in the HB-NSC group from 6-10 weeks compared to the control group (p<0.05). [$^{18}F$]-FP-CIT microPET at 10 weeks posttransplantation demonstrated a significant increase in uptake in the HB-NSC group compared to pretransplantation (p<0.05). In IHC and IF staining, tyrosine hydroxylase and human ${\beta}2$ microglobulin (a human cell marker) positive cells were visualized at the transplant site. Conclusion : These results suggest that the HB-NSC aggregates can survive in the striatum and exert therapeutic effects in a PD model by secreting dopamine.