쿠싱증후군 환자에서 당 대사 이상 정도에 따른 인슐린 감수성과 인슐린 저항성의 변화

정인경,김성훈,정재훈,민용기,이명식,이문규,유형준,안규정,노정현,김동준,김광원 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.4

연구배경 당질 코르티코이드는 당 대사에 매우 중요한 호르몬으로 내인성 당질 코르티코이드 과다상태인 쿠싱증후군에서는 말초조직에서 인슐린 저항이 증가하고 이를 보상하고자 인슐린 분비의 증가로 고인슐린혈증이 동반된다고 보고되고 있다. 하지만 생체 내에서와 달리 시험관내에서는 췌도세포에 당질 코르티코이드를 장시간 처리하면, 인슐린 분비 및 생합성이직접적으로 억제됨이 확인된 바 있어 쿠싱증후군 환자에서 당뇨병의 원인으로는 아마도 말초조직에서 증가된 인슐린 저항성 뿐 아니라 이를 충분히 보상하지 못하는 췌장에서의 인슐린 분비 저하가 같이 동반되어있지 않을까 하는 가설을 세우게 되었고, 아직까지 당질코르티코이드가 당대사 이상을 일으키는 기전에 대해 쿠싱증후군을 당대사 정도에 따라 인슐린 감수성과 분비능을 분석한 연구는 없었기에 이를 알아보고자 하였다. 방법: 삼성서울병원에서 쿠싱증후군으로 진단 받은 환자 15명을 대상으로 하였다. 이에 대한 대조군으로는 쿠싱증후군 환자와 같은 성별 그리고 체질량지수를 갖은 15명의 건강한 성인을 대상으로 비교 하였다 쿠싱증후군 환자를 대상으로 경구당부하 검사를 통해 당대사 정도를 정상군, 내당능장애군, 그리고 당뇨병군으로 나눈 후 정맥 당부하 검사를 시행하여 각군의 인슐린 저항성과 인슐린 분비능의 지표를 비교하고, 수술 후 쿠싱증후군이 완치된 상태에서 수술 전후의 당대사 지표의 변화를 조사하였다. 결과: 1) 쿠싱증후군 환자 중 정상인은 20%, 내당능 장애는 27%, 그리고 당뇨병은 53%였다. 체질량지수, 나이, 그리고 발병 기간은 세 군간에 의미 있는 차이가 없었으나, 24시간 소변검사의 코르티솔 농도는 당뇨병군에서 의미있게 높았다. 2) 정맥당부하 검사 결과, 인슐린 감수성 지표인 Sl는쿠싱증추린」서 1.58±0.10[×10^(-4)(min^(-1)(μU/mL)^(-1)]로 정상 대조군의 3.37±0.49[×10^(-4)(min^(-1)(μU/mL)^(-1)]에 비해 의미있게 낮았으나(P=0.024), 쿠싱증후군 환자 중 NGT, IGT, DM 군간에 서로 통계적인 차이는 없었다. 3) SG는 정상 대조군과 쿠싱증후군 환자간에는 의미있는 차이가 없었고, 쿠싱 증후군에 있어서 당대사가 악화될수록 감소하는 경향을 보였으나 의미있는 차이는 없었다. 4) 인슐린 분비능의 지표인 AIRg는 정상인에 비해 전체 쿠싱증후군 환자의 경우 증가하는 경향을 보였으나 의미있는 차이는 없었다. 하지만 쿠싱증후군 환자중에서 당대사 상태에 따라 NGT군은 1299 (1297∼1310)(mu/g/min ×10^(-2))로 정상 대조군(368.9±98.6[mu/g/min ×10^(-2)]) 보다도 의미있게 높았고, DM군{202.2 (91.1~371.4) [mu/g/min ×10^(-2)}은 NGT군에 비해 의미있게 낮았다(P=0.0031). 5) 15명중 현재 완치 상태에 있는 6명에 대해 수술전과 후로 비교하였다. 수술 전 당대사 상태가 1명은정상, 1명은 내당능 장애, 그리고 4명은 당뇨병이었으나 수술 후 시행한 경구 당부하 검사상 모두 정상 당대사 상태를 보였다. 6) 수술 후 완치된 환자 6명에 있어 인슐린 감수성지표인 Sl는 수술전에 중앙값이 1.22[×10^(-4)(min^(-1)(μU/mL)^(-1)]로 대조군에 비해 의미있게 감고』어 있었으나(p.0.05), 수술후 10.95 [×10^(-4)(min^(-1)(μU/mL)^(-1)]로 정상 수준으로 회복되었고(P=0.0022), 인슐린 분비능을 나타내는 AIRg [mu/g/min ×10^(-2)] 값도 정상수준으로 회복되었다. 특히 인슐린 분비능의 회복양상은 혈당농도에 따라 판이하게 나타나서, 정상과 내당능장애 상태에 있던 2명은 수술전에 1201 [mu/g/min ×10^(-2)]로 증가되어 있던 AIRg 값이 수술 후 정상 수준으로 감소하였고, 수술 전에 당뇨병 상태에 있던 4명의 경우 245.9 [mu/g/min ×10^(-2)]로 인슐린 분비능이 감고il어 있었는데 이들은 수술 후 모두 정상 수준으로 증가되었다 (P=0.0286). 결론: 쿠싱증후군 환자에서 당대사 이상은 80%로 높은 유병률을 보였다. 모든 쿠싱증후군환자에서 인슐린 감수성은 정상인에 비해 저하되어 있어 말초조직의 인슐린 저항이 선행됨을 시사하며, 인슐린 분비능은 당대사의 정도에 따라 다르게 나타났는데, 정상 당대사군에서는 인슐린의 저항성을 극복할 만큼 정상 대조군보다 더 많은 양의 인슐린 분비를 하다가 고코르티솔혈증이 심할수록 인슐린 분비능의 감소로 당뇨병으로 진행됨을 확인할 수 있었고, 이런 인슐린 저항성과 인슐린 분비장애는 수술 후 다시 회복되는 가역적인변화를 보였다. Background: Glucocorticoid plays an important role in the control of carbohydrate metabolism. Patients with Cushing's syndrome have been reported to have an increased incidence of carbohydrate intolerance due to peripheral insulin resistance and hyperinsulinemia, although the exact incidence and nature of this disorder have remained unclear. Few results have been published about insulin resistance and insulin secretion according to the level of glucose concentration, or about the reversibility of such defects in patients with Cushing's syndrome. Methods: To assess the effect of glucocorticoid on the insulin sensitivity and insulin secretion in Cushing's syndrome, 15 patients with Cushing's syndrome were classified into 3 groups (normal glucose tolerance: NGT, impaired glucose tolerance: IGT, diabetes: DM) according to the degree of glucose tolerance based on the oral glucose tolerance test (OGTT). Insulin modified, frequently sampled, intravenous glucose tolerance test (FSIGT) was performed before and after curative surgery on these patients and on 15 healthy control subjects. Data were evaluated by non-parametric statistical analysis. Results: 1) Among the 15 patients with Cushing's syndrome, 3 (20%) were NGT, 4 (27%) IGT, and 8 (53%) DM, based on OGTT. Twenty-four hour urinary free cortisol (UFC) was significantly higher in the DM group. 2) Insulin sensitivity index (SI) of Cushing's syndrome was significantly lower than that of the control group p=0.0024), but was not significantly different among the three Cushing's syndrome groups of NGT, IGT and DM. 3) Glucose mediated glucose disposal (SG) (Ed- confirm this abbreviation; it does not seem to match the definition) of Cushing's syndrome was not significantly different from that of the control group. 4) Insulin secretion (AIRg) of Cushing's syndrome tended to be high, but it was not significantly different from that of control. However, according to the level of glucose concentration there was significant difference in AlRg among the three Cushing's syndrome groups p=0.0031); AIRg of DM was significantly lower than that of NGT. 5) After surgical treatment, parameters of insulin sensitivity and insulin secretion were normalized in 6 cured patients; 1 with NGT, 1 with IGT, and 4 with DM, preoperatively. Median SI of all 6 patients was significantly improved up to the normal range postoperatively p=0.0022). Median AIRg of these 6 patients was balanced around that of normal control postoperatively p=0.0286). Conclusion: Eighty percent of patients with Cushing's syndrome had abnormality of carbohydrate metabolism. Insulin sensitivity was significantly decreased in Cushing's syndrome. Insulin secretion was significantly higher only in the NGT and IGT groups of Cushing's syndrome. As the hypercortisolemia is exacerbated, insulin secretion is significantly decreased and causes DM, suggesting that glucocorticoid has a direct or indirect toxic effect on the pancreatic beta cell (J Kor SOC Endocrinol 18:392-403, 2003).

담도 및 췌장 악성종양에서의 CAl9-9의 진단적 가치에 대한 평가

명승재,최승목,김은옥,최호순,이성구,김명환,민영일,류진숙 大韓消化器病學會 1995 大韓消化器病學會誌 Vol.27 No.3

개의 췌도분리에서 췌장의 팽창과 콜라겐 분해요소

이상훈,김성주,박정환,김종성,오승훈,한진수,정인경,양태영,김동준,김광원,이문규,민용기,이명식,정재훈,함종렬 대한당뇨병학회 2000 Diabetes and Metabolism Journal Vol.24 No.2

Backgrounds: One of the main problems conditioning the outcome of islet transplantation is the ability to separate a sufficient number of viable islets with preserved function. Islet purification is critically affected by all of the isolation stages. Thus, it is necessary to set up the standard isolation method that islets are separate well from acinar without compromising islet yield and viability. Methods: Twenty three adult mongrel dogs were used for the experiment of total pancreatectomy with islet isolation. The islets were properly isolated by a modified Recordi method. The obtained islets were further purified by centrifugation on discontinuous gradients using cell separation system (Model 2991, Cobe, Lakewood Colo). We evaluated islet number (islet equivalent number, 150 um equivalents/kg of recipient body weight, IEq/kg), purity, cell volume, viabilty, recovery rate, and comparison of outcome according to the isolation conditions. Results: 1) The mean of islet numbers before purification were 13543±9431Eq/kg, digestion times were 13.8±2.6 min., digestion temperature was 37.4±0.2℃, purity was 59.7?.0%, viability was 90.0±2.1%, cell volume was 4.7±1.1 mL, islet number after purification were 4064±361 IEq/kg, and recovery rate was 29±2.9%. 2) Isolated islet numbers were different according to the degree of pancreas distension with collagenase, digestion temperature, and digestion time. 3) The best conditions for islet isolation were above 37.5℃ in temperature at recirculation of collagenase, within 12 min in digestion time and well distended pancreas with collagenase. 4) According to multiple regression adjusted by variable factors, the degree of pancreas distension with collagenase and digestion time were independently associated factors for successful islet isolation. Conclusions: In this study, we concluded that the degree of pancreas distension with collagenase and digestion time were independent factors for successful islet isolation and the best conditions for islet isolation were above 37.5℃ in temperature at recirculation of collagenase, within 12 min in digestion time and well distended pancreas with collagenase.

식품중 중금속 규격 과학화를 위한 조사연구(Ⅲ) : 음료수의 중금속 향량에 대하여 Heavy metal contents beverages

김명철,김미혜,권기성,정소영,박성국,이윤동,이승훈,김은정,강민철,박효정 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

본 연구는 국내에 유통되고 있는 음료류중 중금속 함량을 파악하여 식품공전 제 ·개정시 과학적 기초자료로 활용하고자 수행하였다. 출 2☞7여건의 음료류에 대하여 유도결합플라스마 분광기(ICP), 원자홉광광도 계(AAS) 및 수은분석기 등을 치용하여 납, 카드윰 등 중금속함량을 측정하였으며 그 결과는 다음과 같다 [단위 : min-ma)t(irran) ; mrk3 ; f : 0.0001-0.0025(0.0003), As :불검출곰.OB45(0.0003), Pb : 불검출-0.0893(0.0041),Cd ' 불검출곤.0064(0.0011), Cfl : 불검출.(i9(0.05), Mn : 불검출글.찌(0.16), Zn : 불검출-12.85(0.뽀), Sn :불검출-45.36(1.97). 본 조사결과 우리나라에서 유통되고 있는 음료류 중 납 등 중금속 함량은 외국의 모니터랑 결과와 유사하였다. 또한 우리나라 국민이 음료류를 통한 중금속 섭취량은 FAO/UTfO에서 설정한 잠 정주간섭취처용량의 약 0.OleO.06% 이하로 매우 낮았다. 편 연구조사에서 먼어진 결과는 음료류 중 납 기준 설정을 위한 중요한 기초자료로 활용할 수 있는 것으로 사료된다. This study was conducted to estimate the cantents of heavy netals in beverages and to fIFovide a scientific basis for heav)· meta3 standardizatior of Korea Food Code. The contents of rriercur17(Hg), lead(Pb), cadmium(Cd), arsenic(As), manganese(Mn),ziac(Zn), tin(Sn) and topper(Cu) were determined in a total of 20? samples of beverages usinga mercury anal!'zer, aromic absorption spectrophotometer(AAS) and inductiuety coupled plasmaspectrometer(fcpl. The vatues of heavy metals In beverages were as fellows (min-max (mean) , mg/krl , Hg : 0.DOOI-0.0095(0.0004), As : ND-0.0245(0.0003), Pb ND-0.0893(0.0041), Cd : ND-0.0064(0.0011),Cu : ND-1.69(0.03), Mn : ND-3.94(0.16), Zn ND-12.85(0.28), Sn : ND-45.36(1,97). Our results weresimilar to thofe reported by other countries. It is thought that our results could be utilizedimportant references toT es?ablish the standard of lead in beverages.

H9c2 심근 세포주에서 외인성 nitric oxide가 허혈에 의한 세포 독성에 미치는 영향

정성구,장현용,김명천,고영관,정주호,배영미,박원서,김대중,유영민,김성수,임성빈 대한응급의학회 2001 대한응급의학회지 Vol.12 No.4

Background: Nitric oxide(NO) is known to have protective effects on an ischemic heart and to exert triggering effects on ischemic preconditioning. However, the effects of NO during the ischemic period have not been investigated. To investigate the role of exogenous nitric oxide in a model of ischemic heart cell death, we studied the effects of ischemic preconditioning and ischemia in a normal and an ischemic buffer. Methods: Rat cardiac myoblast cells(H9c2) were cultured in a normal and an ischemic buffered medium. For the ischemic culture of heart cells, the cells were cultured in a dessicator with GasPak for 5 hrs. In ischemic preconditioning, the cells were pretreated with ischemic buffer for 5 min and then perfused with normal medium for 30 min. For the measurement of the cytotoxicity, a MTT(3-4-Sdimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide) assay was performed. A DAPI(4',6-diamidino-2-phenylindole dihydrochloride) staining procedure and a flow cytometry analysis were performed to confirm apoptotic cell death by ischemia. Results: Cell viability, as determined by using a MTT assay, showed that the preconditioned group treated with NO showed more cell death than with the not-preconditioned groups in both normal and ischemic buffers. But, In normal medium and not-preconditioned groups, NO showed protective effect according to the concentrations(100,1000μM) . No treatment with NO produced the different results. In normal medium, the protective effect of ischemic preconditioning was demonstrated, but no protective effect of ischemic preconditioning could be seen in the case of the ischemic buffer. The DAPI staining and flow cytometry analysis of heart cells showed characteristic apoptotic features. Conclusion: NO added in the ischemic phase had deterious effects on heart cells. Ischemic preconditioning was more harmful than ischemia alone. The toxicity of the cells was characteristic apoptosis.

주산기 백서에서 혈중 에스트로겐 농도와 공간 기억력과의 상관관계

박민성,박제민,신성현,한귀원,김명정,김성곤 大韓神經精神醫學會 2006 신경정신의학 Vol.45 No.5

Objectives : This study was designed to find possible effect of pregnancy and parturition on spatial memory, especially in relation to levels of estrogen during the third trimester and postpartal period in rats. Methods : 25 female Sprague Dawley rats were divided into pregnant group (N= 14) and control group (N= 11). Changes in spatial memory during 6 weeks including third trimester and postpartal period were measured using Morris water maze. Time to reach the platform in the maze was indicator of spatial memory. Serum estrogen level was measured on 1 week before delivery, postpartal day 1, and day 14. Results : Both groups showed gradual improvement in performance by trial days and weeks, but no significant difference was found between the two groups. However in the third trimester, pregnant group showed a trend of less achievement on 3 days of learning than control group. Serum estrogen levels did not differ significantly between groups over the 6 weeks of period. However there was positive correlation between serum estrogen level on postpartum day 1 and time to reach platform on postpartum week 2, and negative correlation between estrogen level on postpartum day 14 and latency to the platform on postpartum week 5. Conclusion : These results imply that changes in the serum estrogen level may have dual effects on the spatial learning in peripartal period. It is suggested that decline in cognitive function might occur either by failure of rapid decrease of estrogen, immediately after parturition, or retarded restoration of estrogen in later postpartal period.

Differential Effects of Pioglitazone in the Hippocampal CA1 Region Following Transient Forebrain Ischemia in Low- and High-Fat Diet-Fed Gerbils.

Moon, Seung Myung,Choi, Goang-Min,Yoo, Dae Young,Jung, Hyo Young,Yim, Hee Sun,Kim, Dae Won,Hwang, In Koo,Cho, Byung Moon,Chang, In Bok,Cho, Sung-Min,Won, Moo-Ho Kluwer Academic/Plenum Publishers 2015 Neurochem Res Vol.40 No.5

<P>In the present study, we investigated the effects of pioglitazone (PGZ) in the hippocampal CA1 region of low- or high-fat diet (LFD or HFD) fed gerbils after transient forebrain ischemia. After 8 weeks of LFD or HFD feeding, PGZ (30 mg/kg) was intraperitoneally administered to the gerbils, following which ischemia was induced by occlusion of the bilateral common carotid arteries for 5 min. Administration of PGZ significantly reduced the ischemia-induced hyperactivity 1 day after ischemia/reperfusion in both LFD- and HFD-fed gerbils. At 4 days after ischemia/reperfusion, the neurons were significantly reduced and microglial activation was observed in the hippocampal CA1 region in LFD- and HFD-fed gerbils. The microglial activation was more prominent in the HFD-fed gerbils compared to the LFD-fed gerbils. Administration of PGZ ameliorated ischemia-induced neuronal death and microglial activation in the hippocampal CA1 region 4 days after ischemia/reperfusion in the LFD-fed gerbils, but not in the HFD-gerbils. At 6 h after ischemia/reperfusion, tumor necrosis factor-α (TNF-α) and interlukin-1β (IL-1β) levels were significantly increased in the hippocampal homogenates of LFD-fed group compared to control group, and HFD feeding further increased TNF-α and IL-1β levels. PGZ treatment significantly ameliorated the increase of TNF-α and IL-1β levels in LFD-fed gerbils, not in the HFD-fed gerbils. At 12 h after ischemia/reperfusion, superoxide dismutase (SOD) and malondialdehyde (MDA) levels in hippocampal homogenates were significantly increased in the LFD-fed group compared to the control group, and HFD feeding significantly showed relatively reduction in SOD activity and increase in MDA level. PGZ administration significantly reduced the increase in MDA levels 12 h after ischemia/reperfusion in the LFD-fed gerbils, but not in the HFD-fed gerbils. These results suggest that PGZ ameliorates the neuronal damage induced by ischemia by maintaining the TNF-α, IL-1β, SOD and MDA levels in LFD-fed gerbils. In addition, HFD feeding affects the modulation of these parameters in the hippocampus after transient forebrain ischemia.</P>

사회적 음주자에서 날트렉손 투여가 급성 음주 반응에 미치는 영향

김종현,김성곤,신성현,박제민,김명정 大韓神經精神醫學會 2004 신경정신의학 Vol.43 No.6

Objectives : We investigated the effects of naltrexone on acute alcohol response, stimulant and sedative, in healthy social drinkers using two doses of alcohol intake. Methods : Twenty four healthy male medical students were voluntarily participated. The experimental method was Cross-over design, Subjects received 25 mg/day or 50 mg/day of naltrexone on the experimental days. Biphasic Alcohol Effects Scale (BAES), alcohol craving, and blood alcohol concentration (BAC) were measured before drinking and at 15, 30, 45, 60, 90,and 120 min after drinking. Results : 1) Group of 0.6 mg/kg of alcohol intake. When the scores of stimulative subscale of BAES were compared bet-ween the naltrexone and control group, the scores were significantly lower in the naltrexone group at 15 and 90 min after drinking. Alcohol induced sedative effect was significantly higher in the naltrexone group at 90 min after drinking. The alcohol induced alcohol craving at 45 and 60 min after drinking was significantly lower in the naltrexone group as compared to the control. 2) Group of 0.3 ing/kg of alcohol intake. The alcohol induced stimulative effect evident in the control group seen in the time span of 15 to 45 min after drinking was not seen in the naltrexone group. The increase of alcohol induced alcohol craving noticed at 30 min after drinking in the control group was not seen in the naltrexone group. BAC at 15 min after drinking was lower in the naltrexone group compared to the control. Conclusion : Naltrexone is suggested to attenuate stimulative effect, to intensify sedative effect, and to block alcohol induced alcohol craving. These triple actions might be utilized for treatment and prevention of relapse of alcohol dependence.

허혈성 심질환에 있어서 아데노신 급속 정맥투여후 관동맥압의 변화에 관한 연구

봉종대,오종용,배성한,신원용,김철현,이광희,최태명,현민수,김성구,권영주 순천향의학연구소 1998 Journal of Soonchunhyang Medical Science Vol.4 No.2

Background: Adenosine interacts with A1 receptors present on the extracellular surface of cardiac cells, activating K+channels in a fashion. It produces coronary vasodilatation and AV nodal block. The half-time is one to six second and has ultra-short action. In ischemic heart disease, fractional flow reserve(FFR) can be achieved safely with intravenous adenosine infusions at a rate of 150㎍/kg/min which cause maximal coronary hyperemia. Purpose: We investigated the patients who have had ischemic heart disease(n=8). After adenosine intravenous administration(150㎍/kg/min), the effect cause maximal hyperemia of coronary artery. During peak maximal hyperemia, we reported clinical findings, coronary hemodynamics and electrocardiogram findings. Methods: After diagnostic coronary angiography and left ventriculography, catheter was advanced into the ostium of coronary artery. We investigated coronary hemodynamics such as systolic coronary artery pressure, diastolic coronary artery pressure, mean coronary artery pressure and heart rate. To assess the use of adenosine for determination of fractional flow reserve, hemodynamics and electrocardiogram were measured at basal state and during peak maximal hyperemia. Results: Symptoms developed 1.5-2 minute after adenosine intravenous administration and each symptom disappeared 2-2.5 minute after adenosine administration. Two patients represented asymptomatic appearance and six patients complained of flushing, chest pain, palpitation and headache. In eight patients with ischemic heart disease, 1.5 minute after venous administration of 150㎍/kg/min of adenosine, coronary artery pressure decreased and heart rate increased significantly. Conduction abnormalities after administration of 150㎍/kg/min of adenosine were transient 2nd degree AV block 2 cases(25%). Conclusions: Adenosine is a potent ultra short-acting vasodilator. Although coronary artery pressure decreased and heart rate increased and mild cardiovascular symptoms occurred after continuous infusion of 150㎍/kg/min of adenosine, it is useful as an agent for determination of fractional flow reserve.

벤조디아제핀 수용체 영상용 양전자 방출 핵종 표지 플루마제닐 유도체 [F-18](3-(2-Fluoro)flumazenil의 합성과 생체 내 분포

장영수,이숙자,강삼식,홍성현,이명철,이동수,정준기,정재민,조정혁 대한핵의학회 1999 핵의학 분자영상 Vol.33 No.6

Purpose: Radiotracers that bind to the central benzodiazepine receptor are useful for the investigation of various neurological and psychiatric diseases. [C-11]Flumazenil, a benzodiazepine antagonist, is the most widely used radioligand for central benzodiazepine receptor imaging by PET. We synthesized 3-(2-[F- 18]fluoro)flumazenil, a new fluorine-18 (t1/2=110 min) labeled analogue of benzodiazepine receptor imaging agent, and evaluated in vivo for biodistribution in mice. Materials and Methods: Flumazenil (Ro 15-1788) was synthesized by a modification of the reported method. Precursor of 3-(2-[F-18]fluoro)flumazenil, the tosylated flumazenil derivative was prepared by the tosylation of the ethyl ester by ditosylethane. [F-18] labeling of tosyl substitued flumazenil precursor was performed by adding F-18 ion at 85℃ in the hot cell for 20 min. The reaction mixture was trapped by C18 cartridge, washed with 10% ethanol, and eluted by 40% ethanol. Bidistribution in mice was determined after intravenous injection Results: The total chemical yield of tosylated flumazenil derivative was ∼40%. The efficiency of labeling 3-(2-[F-18]fluoro)flumazenil was 66% with a total synthesis time of 50 min. Brain uptakes of 3-(2-[F-18]fluoro)flumazenil at 10, 30, 60 min after injection, were 2.5±0.37, 2.2±0.26, 2.1±0.11 and blood activities were 3.7±0.43, 3.3±0.07, 3.3±0.09%ID/g, respectively. Conclusion: We synthesized a tosylated flumazenil derivative which was successfully labeled with no-carrier-added F-18 by nucleophilic substitution.