补充支链氨基酸对运动大鼠脑及血小板5-HT2A受体与螺环哌丁苯结合影响的研究

采用放射标记受体测定技术观察补充支链氨基酸 (BCAA)或BCAA +CHO对SD大鼠一次性运动以及 3周耐力训练后的一次性运动前后血小板以及脑 5 -HT2A受体与 [3H]Spiperone(螺环哌丁苯 )结合的影响 ,结果表明 :急性耐力运动可导致SD大鼠脑 5 -HT浓度的增加 ,并且导致血小板以及脑 5 -HT2A受体下调 ,大鼠 3周耐力训练期间补充BCAA +CHO有防止由耐力运动引起的 5-HT2A受体密度下调的作用 ,长期耐力训练期间补充BCAA +CHO对延缓中枢疲劳有积极的作用。     

5-HT2A受体在腹外侧眶额皮质参与口面部疼痛的研究

目的 研究腹外侧眶额皮质5-HT2A受体表达水平对福尔马林诱导的口面部炎性痛发生的影响,揭示5-HT2A受体参与口面部疼痛的机制.方法 将6～8周龄C57BL雄性小鼠随机分为野生型组(WT组)、空载体组(NC组)、5-HT2A受体敲减组(KD组);腹外侧眶额皮质注射腺病毒建立小鼠5-HT2A受体敲减模型;4周后采用We...     

以5-HT1A受体为靶标的抗抑郁药物研究进展

5-HT1A受体是含量最丰富的5-HT受体亚型,广泛分布于脑内,与抑郁症关系密切。抑郁症患者的5-HT1A受体表达异常,改变5-HT1A受体表达则影响抗抑郁治疗的效果;联合应用5-HT1A受体激动剂与选择性5-HT重摄取抑制剂（SSRIs）能够增强SSRIs的抗抑郁作用,缩短起效时间。近年研究发现,5-HT1A受体转录调控区C（-1019）G基因多态性与抑郁症的发病相关,并影响抗抑郁药物的效应。该文综述了5-HT1A受体在抑郁症发生和治疗中的作用及其作为药物研发新靶点的研究进展。     

5-HT_（1A）受体激动和5-HT重摄取抑制双靶标新药YL-0919抗抑郁作用的药效学评价

目的评价兼有5-HT1A受体激动和5-HT重摄取抑制双靶标化合物YL-0919的抗抑郁作用,并在靶标水平探讨其作用机制。方法和结果在小鼠悬尾和小鼠强迫游泳实验中,YL-0919（1.25,2.5,5 mg/kg,ig）能够显著地缩短小鼠悬尾不动时间和游泳不动时间,5-HT1A受体拮抗剂WAY100635（0.3 mg/kg,sc）能够完全拮抗YL-0919（2.5 mg/kg,ig）在小鼠悬尾实验中的抗抑郁作用;在药物诱发抑郁模型上,YL-0919增强5-羟色氨酸（5-hydroxytryptophan,5-HTP,120 mg/kg,ip）诱导的小鼠甩头行为,但不能拮抗高剂量阿扑吗啡（16 mg/kg,sc）诱导的降温作用;YL-0919在抗抑郁有效剂量范围内对小鼠的自主活动性无显著性影响。结论新型双靶标新药YL-0919具有明确的抗抑郁作用,此作用与激动5-HT1A受体,增强5-HT系统的功能有关。     

5-HT1A受体显像剂18F-MPPF的制备及其生物学特性评价

目的　探讨 5 羟色胺 (5 HT1A)受体显像剂 4 1 8F N 2 [1 (2 甲氧基苯基 ) 1 哌嗪基乙基 ] N 2 吡啶基 苯甲酰胺 (1 8F MPPF)的1 8F标记方法及其生物学特性。方法　以氟化聚铵 (kryptofix K 1 8F)为亲核试剂 ,在二甲亚砜 (DMSO)溶液中与 4 (2′ 甲氧基 苯基 ) 1 [2′ (正 2″ 吡啶基 ) 对硝基苯甲酰胺 ] 乙基哌嗪 (MPPNO2 )进行氟代亲核置换反应 ,用HPLC检测放射化学纯度 (RCP) ;进行1 8F MPPF大鼠脑内分布和阻断实验、大鼠脑放射自显影及异常毒性实验。结果　HPLC检测示1 8F MPPF与杂质分离好 ,RCP >95 % ;大鼠脑内分布实验表明 ,放射性在脑内不同区域的清除速率不同 ,小脑清除最快 ,海马最慢 ,海马每克组织百分注射剂量率 (%ID g)在注药后 2 ,30和 6 0min分别为 0 86 2 ,0 196和 0 0 4 8,注药后 30min ,海马特异结合 [(T CB) - 1]可达 2 70 ;预先给予 8 羟基 2 N ,N′ (双正丙基 )氨基四氢萘(8 OH DPAT)、4 (2′ 甲氧基 苯基 ) 1 [2′ (正 2″ 吡啶基 ) 环己烷碳酰胺 ] 乙基哌嗪 (WAY10 0 6 35 )和螺环哌啶酮 (Spiperone)后 ,海马 (T CB) - 1分别降至 0 89,0 74和 1 93;放射自显影示 ,1 31 I 4 (2′ 甲氧基 苯基 ) 1 [2′ (正 2″ 吡啶基 ) 对碘苯甲酰胺 ] 乙基哌嗪 (MPPI     

5-HT1A受体与抑郁症相关性研究

抑郁症的发病机制复杂,确切发病机制尚不清楚,目前普遍认为可能是心理社会因素、各种神经生物化学改变、遗传因素等多种因素交互作用的结果,其中神经生化改变是迄今最为肯定的,并成为临床治疗抑郁症的理论基础.脑内中枢去甲肾上腺素（NE）、5-羟色胺（5-HT）、多巴胺（DA）等单胺类神经递质含量过低、其受体功能低下、下丘脑-垂体-肾上腺轴（HPA）和下丘脑-垂体-甲状腺轴（HPT）等神经生化的改变都被认为是引起抑郁症的原因.近年来选择性5-HT受体激动剂类抗抑郁药的研究揭示5-HT1A受体是重要的作用靶点.现就5-HT1A受体与抑郁症相关性研究进展作一综述.     

谷氨酸对腺苷A2A受体调节一氧化氮合酶活力的影响

目的探讨谷氨酸是否能够影响腺苷A2A受体对一氧化氮合酶（NOS）活力的调节。方法用1000ng／ml脂多糖（LPS）刺激小胶质细胞，分别加入100nmol／L A2A受体激动剂CGS21680以及不同浓度的谷氨酸（0，1，0，25，0，5mmol／L）干预，观察NOS活力变化。结果LPS诱导NOS活力增高，激活A2A受体可以产生抑制作用；0，25及0．5mmoL／L谷氨酸和A2A受体激动剂同时存在时，NOS活力进一步增高。结论高浓度谷氨酸可逆转腺苷A2A受体激动剂抑制升高NOS活力的作用。     

补充支链氨基酸对划船运动员不同负荷运动后血丙氨酸、葡萄糖及乳酸的影响

目的:探讨补充支链氨基酸(BCAA)对划船运动员不同负荷运动后及恢复期糖代谢和糖异生的影响.方法:20名划船运动员随机分为补充BCAA组和对照组,补充BCAA组每天补充BCAA胶囊(每粒含缬氨酸300mg, 亮氨酸250mg,异亮氨酸100mg),3次/日,4粒/次,对照组补充安慰剂.实验期间,两组运动员均进行相同负荷训练.4周后,在赛艇测功仪上分别进行递增有氧负荷实验(4mmol/L血乳酸)和模拟2km和5km极限负荷测试,分别在运动前、运动后即刻和运动后30min取血,测定血糖、血乳酸和丙氨酸水平.结果:在无氧阈测试中,两组运动员血乳酸和丙氨酸浓度在运动即刻和恢复期较安静时均明显增高(P<0.05),血糖则无明显变化(P>0.05),且两组间无显著性差异.在极限负荷运动中,补充BCAA组运动后即刻血糖显著低于安静水平(P<0.05),对照组运动后即刻和运动后30min均显著低于安静水平(P<0.05).补充BCAA组运动员血丙氨酸浓度运动后即刻和运动后30min均较对照组和安静水平明显增加 (P<0.05),而对照组运动后即刻显著低于安静水平(P<0.05).补充BCAA组运动后血乳酸显著低于对照组(P<0.05).提示:补充BCAA能促进极限运动后及恢复期糖异生,延缓疲劳发生和促进运动后疲劳的消除.     

外周血白细胞腺苷A2A受体缺失对慢性低灌注性脑白质损伤的影响

目的 观察外周血白细胞腺苷A2A受体缺失对慢性低灌注性脑白质损伤的影响.方法 γ射线照射雄性野生型(WT)小鼠清髓,尾静脉注射雌性A2A受体基因敲除(KO)小鼠的骨髓细胞者作为KO→WT组(n=24),注射雌性WT小鼠骨髓细胞者作为WT→WT组(n=20).7周后对接受骨髓移植小鼠的外周血白细胞进行性染色体基因型鉴定以及A2A受体荧光染色,以评价移植效果.8周后制作慢性脑血流低灌注模型.成模7,14d和30d取胼胝体、Caudoputamen纤维束、视柬3个白质区域的脑组织,进行Klu-ver-Barrera染色,观察神经纤维改变;行GFAP、CD11b免疫组化染色观察胶质细胞增生程度.结果 基因型鉴定发现移植7周后雄性受体小鼠外周血白细胞性染色体基因型为雌性,且KO→WT组小鼠外周血白细胞A2A受体阳性率(9.73%±2.05%)较WT→WT组(93.82%±11.24%)显著下降(P<0.01).建模后14d和30d,KO→WT组小鼠脑白质区域神经纤维稀疏程度显著重于WT→WT组(P<0.01),同时.前者胼胝体和Caudoputamen纤维束区域胶质细胞数目较后者显著增多(P<0.01).结论 外周血白细胞A2A受体缺失会加重慢性低灌注性脑白质损伤,提永外周血白细胞A2A受体可能对中枢神经系统损伤有重要调节作用.     

耐力训练及补充中药多糖提取物对大鼠白细胞介素2及受体水平的影响

目的:探讨6周耐力训练及补充多糖提取物对大鼠白细胞介素2及受体水平的影响.方法:120只雄性Wistar大鼠随机分为6组:耐力训练 黄芪多糖组、耐力训练 牛膝多糖组、单纯耐力训练组、安静 黄芪多糖组、安静 牛膝多糖组和安静对照组.每组又均分为4周组(7只大鼠)和6周组(13只大鼠).6周递增负荷游泳训练后,观察大鼠白细胞介素2及受体水平的改变.结果:(1)6周耐力训练可造成大鼠血清IL-2、T细胞mIL-2Rα表达下降(P均小于0.05)和sIL-2R升高(P<0.01).(2)6周耐力训练同时补充黄芪多糖和牛膝多糖提取物能防止大鼠血清IL-2、T细胞mIL-2Rα表达明显下降及sIL-2R升高.结论:黄芪多糖和牛膝多糖可通过调节IL-2及其受体发挥对耐力训练大鼠细胞免疫的调节作用.     

选奇滴丸对偏头痛动物模型血清中NO 5-HT浓度的影响

目的观察选奇滴丸对偏头痛大鼠血清中一氧化氮、五羟色胺浓度的影响,探讨选奇滴丸治疗偏头痛的机制。方法 Wistar大鼠随机分为6组：空白对照组、模型对照组、阳性药物对照组（正天丸2 g·kg-1）、选奇滴丸低、中、高剂量组（0.29、0.59、1.18 g·kg-1）,各组连续灌胃给药7 d（空白对照组与模型对照组给予等量纯净水）,末次给药30 min后,除空白对照组外,其余各组采用皮下注射硝酸甘油法制备偏头痛模型。造模4 h后腹主动脉采血,采用硝酸酶还原法测定一氧化氮浓度,酶联免疫吸附法测定五羟色胺含量。结果与模型对照组比较,阳性药物对照组,选奇滴丸低、中、高剂量组均能显著降低偏头痛大鼠血清中一氧化氮浓度,升高血清中五羟色胺浓度。结论选奇滴丸治疗偏头痛与其调节偏头痛大鼠一氧化氮与五羟色胺的水平密切相关。     

Synthesis and in vivo evaluation of [O-methyl-11C](2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy]ethyl-1-methylpyrrolidine as a 5-HT2A receptor PET ligand

The serotonin2A (5-HT2A) receptor is implicated in the pathophysiology of schizophrenia and mood disorders, and in vivo studies of this receptor would be of value in studying the pathophysiology of these disorders and in measuring the relationship of clinical response to receptor occupancy for 5-HT2A antagonists such as atypical antipsychotics. Therefore, (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)-phenyl]ethyl]phenoxy]ethyl-1-methylpyrrolidine (MPM) (13), a selective and high-affinity (K(i)=0.79 nM) 5HT2A antagonist, has been radiolabeled with carbon-11 by O-methylation of the corresponding desmethyl analogue (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-hydroxy)phenyl]ethyl]phenoxy]ethyl-1-methylpyrrolidine (12) with [11C]methyltriflate in order to determine the suitability of [11C]MPM to quantify 5-HT2A in living brain using PET. Desmethyl-MPM 12 and standard MPM were prepared, starting from 3-hydroxymethylphenol (2), in excellent yield. The yield obtained for radiolabeling was 40+/-5% (EOB), and the total synthesis time was 30 min at EOS. PET studies with [11C]MPM in baboon showed a distribution in the brain consistent with the known distribution of 5-HT2A receptors. The time-activity curves for the high-binding regions peaked at approximately 45 min after injection. Blocking studies with M100907 demonstrated not only 38-57% blocking of tracer binding in brain regions known to have 5-HT2A receptors but also 38% blocking in cerebellum, which has a low 5-HT2A receptor concentration. Although [11C]MPM exhibits appropriate kinetics in baboon for imaging 5-HT2A receptors, its specific binding in cerebellum and higher proportion of nonspecific binding limit its usefulness for the in vivo quantification of 5-HT2A receptors with PET.     

经皮穴位电刺激对跑台运动大鼠血浆氨基酸及中缝背核细胞外液5-HT含量的影响

目的:探讨经皮穴位电刺激(TEAS)对急性跑台运动大鼠血浆氨基酸及中缝背核(DRN)细胞外液5-HT含量的影响。方法:20只雄性SD大鼠行DRN立体定位术后,随机分为运动组(n=10)和TEAS组(n=10)。术后第2天,所有大鼠开始接受适应性运动,TEAS组介入TEAS治疗,取右侧足三里穴进行电针治疗,参数为连续波,频率2Hz,强度5mA,时间30min,每日1次,连续治疗6天。术后第7天,行微透析采样,收集基础液后进行急性跑台运动(先以10m/min的速度运动10min,在随后4min内将跑速调至24m/min并持续运动1h,坡度为0),微透析采样直至运动后5h。记录运动中毛刷刺激频次;采用脑微透析采样技术和高效液相电化学法(HPLC-ECD)连续观察运动前后大鼠DRN细胞外液5-HT水平动态变化;运动后5h时,采用高效液相紫外法(HPLC-UV)检测血浆氨基酸含量。结果:(1)TEAS组毛刷刺激频次显著低于运动组(P<0.05)。(2)与运动组比较,TEAS组大鼠血浆总色氨酸(T-TRP)和支链氨基酸(BCAA)含量变化不明显(P>0.05),而血浆游离色氨酸(f-TRP)含量(P<0.01)、f-TRP/T-TRP(P<0.01)和f-TRP/BCAA比值(P<0.05)显著降低。(3)运动组运动后即刻DRN细胞外液5-HT水平显著高于基础水平(P<0.05),在随后2h内降低,而在运动后3h和4h时又呈升高趋势,显著高于运动后2h时;TEAS组在运动后各时段均低于运动组,尤以运动后5h为显著(P<0.05)。结论:TEAS足三里穴可有效提高大鼠运动能力,可能通过降低血浆TRP游离度和f-TRP转运入脑,进而减少脑内5-HT的部分合成实现的。     

In vivo delineation of 5-HT1A receptors in human brain with [18F]MPPF.

Serotonin-1A (5-hydroxytryptamine-1A [5-HT1A]) receptors have been reported to play an important role in the pathophysiology of a variety of psychiatric and neurodegenerative disorders. Animal experiments have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2'-pyridinyl)-p-[18F]fluorobenzamido ]ethylpiperazine ([18F]MPPF) may be suitable for 5-HT1A receptor imaging in humans. The aim of this study was to determine if [18F]MPPF can be used for the quantitative analysis of 5-HT1A receptor densities in brain regions of healthy human volunteers. METHODS: [15O]H2O perfusion scanning was performed before intravenous injection of [18F]MPPF to obtain anatomic information. Cerebral radioactivity was monitored using a PET camera. Plasma metabolites of [18F]MPPF were determined by high-performance liquid chromatography. Binding potentials were calculated using the metabolite-corrected arterial input function and a linear graphic method (Logan-Patlak analysis). RESULTS: The highest levels of radioactivity were observed in the medial temporal cortex, especially in the hippocampal area. In contrast, the cerebellum and basal ganglia showed low uptake of 18F, in accordance with known 5-HT1A receptor distribution. The calculated binding potentials correlated well with literature values for 5-HT1A receptor densities. The binding potentials for [18F]MPPF were 4-6 times lower than those that have been reported for [carbonyl-1C]-(N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyrid yl) cyclohexane-carboxamide (WAY 100635), indicating that [18F]MPPF has a lower in vivo affinity for 5-HT1A receptors. CONCLUSION: These results confirm that [18F]MPPF can be used for the quantitative analysis of 5-HT1A receptor distribution in the living human brain. The rapid dissociation from the receptor makes this ligand a possible candidate to monitor changes in endogenous serotonin levels.     

Characterization of radioactive metabolites of 5-HT2A receptor PET ligand [18F]altanserin in human and rodent

This study was performed to identify and characterize the radiometabolites of the serotonin 5-HT2A receptor ligand [18F]altanserin in supporting quantification of the target receptors by positron emission tomography. In analogy to its analog ketanserin, we postulated 4-(4-fluorobenzoyl)piperidine (FBP) and altanserinol for the previously observed two polar radiometabolites, corresponding to dealkylation at the piperidine nitrogen and reduction at the ketone, respectively. To test this hypothesis and characterize the in vivo and in vitro behavior of the radiometabolites, we synthesized nonradioactive authentic compounds altanserinol, 1-(4-fluorophenyl)-1-(piperidin-4-yl)methanol (FBPOH), and isolated nonradioactive FBP metabolite from monkey plasma. [18F]Altanserinol was obtained by NaBH4 reduction of [18F]altanserin, followed by acid hydrolysis. Identification of radiometabolites was carried out by high performance liquid chromatography and thin layer chromatography comparison of the radioactive plasma after injection of tracers with five authentic compounds. Human studies revealed that at least four radiometabolites, one identified as [18F]altanserinol, resulted from reduction of the ketone functionality. The N-dealkylation product [18F]FBP was not detectable; however, a radiometabolite of FBP was present in plasma after administration of [18F]altanserin. Monkey studies showed nonradioactive FBP was converted rapidly to a less polar metabolite. In rat, altanserin and altanserinol were converted to each other in vivo, and all the radiometabolites likely penetrated the blood-brain barrier and entered the brain. Displacement binding of altanserin to cloned serotonin 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors showed Ki values of 0.3, 6.0, 1,756, and 15 nM; the binding of FBP and altanserinol to these four 5-HT subtypes was negligible. We conclude from these studies that the radiometabolites of [18F]altanserin from N-dealkylation and ketone reduction should not interfere with specific receptor quantification in an equilibrium paradigm.     

PET quantification of 5-HT2A receptors in the human brain: a constant infusion paradigm with [18F]altanserin.

[18F]altanserin has been used to label serotonin 5-HT2A receptors, which are believed to be important in the pathophysiology of schizophrenia and depression. The purpose of this study was to test the feasibility of a constant infusion paradigm for equilibrium modeling of [18F]altanserin with PET. Kinetic modeling with [18F]altanserin may be hampered by the presence of lipophilic radiometabolites observed in plasma after intravenous administration. METHODS: Eight healthy volunteers were injected with [18F]altanserin as a bolus (208+/-9 MBq [5.62+/-0.25 mCi]) plus constant infusion (65+/-3 MBq/h [1.76+/-0.08 mCi/h]) ranging from 555 to 626 min (615+/-24 min) after injection. PET acquisitions (10-20 min) and venous blood sampling were performed every 30-60 min throughout the infusion period. RESULTS: Linear regression analysis revealed that time-activity curves for both brain activity and plasma [18F]altanserin and metabolite concentrations stabilized after about 6 h. This permitted equilibrium modeling and estimation of V3' (ratio of specific uptake [cortical-cerebellar] to total plasma parent concentration after 6 h). Values of V3' ranged from 1.57+/-0.38 for anterior cingulate cortex to 1.02+/-0.39 for frontal cortex. The binding potential V3 (ratio of specific uptake to free plasma parent concentration after 6 h, using group mean f1) was also calculated and ranged from 169+/-41 for anterior cingulate cortex to 110+/-42 for frontal cortex. From 6 h onward, the rate of change for V3' and V3 was only 1.11+/-1.69 %/h. CONCLUSION: These results demonstrate the feasibility of equilibrium imaging with [18F]altanserin over more than 5 radioactive half-lives and suggest a method to overcome difficulties associated with lipophilic radiolabeled metabolites. The stability in V3 and V3' once equilibrium is achieved suggests that a single PET acquisition obtained at 6 h may provide a reasonable measure of 5-HT2A receptor density.     

Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C] acetate and [18F]FDG in cultured prostate cancer cells

IntroductionCholine, acetate and glucose ([2-¹⁸F]fluoro-2-deoxyglucose, [¹⁸F]FDG) analogs are under investigation as positron emission tomography (PET) tracers for the imaging of prostate cancer; however, their response to tumor hypoxia has not been clarified.MethodsThe uptake of [methyl-³H]choline, [1-¹⁴C]acetate and [¹⁸F]FDG was monitored in androgen-independent PC-3 cells and androgen-sensitive LNCaP cells under aerobic or anoxic conditions. The effect of androgen depletion was also examined.ResultsPC-3 cells exhibited aerobic choline and acetate uptake five to six times higher than FDG uptake, whereas LNCaP cells showed choline uptake 2.2-fold higher than acetate uptake and 10-fold higher than FDG uptake. After 4 h of anoxia, PC-3 cells showed an 85% increase in FDG uptake, a 15% decrease in choline uptake and a 36% increase in acetate uptake, whereas LNCaP cells showed a 212% increase in FDG uptake, a 28% decrease in choline uptake and no change in acetate uptake. Androgen depletion resulted in a marked decrease in the uptake of all tracers in LNCaP cells but no changes in PC-3 cells.ConclusionIn aerobic conditions, both PC-3 and LNCaP cells exhibited an order of uptake preference as follows: choline>acetate>FDG. In hypoxic cells, the order is reversed, reflecting diverse biochemical responses to hypoxia. These findings may help to explain PET imaging findings of the diverse responses of these tracers in different stages and locations of prostate cancer. Androgen depletion markedly suppressed the uptake of all three tracers in LNCaP cells, which suggests the potential for underestimation of the disease state when PET imaging is performed subsequent to antiandrogen therapy.     

Transport mechanisms of 3-[123I]iodo-alpha-methyl-L-tyrosine in a human glioma cell line: comparison with [3H]methyl]-L-methionine.

The amino acid analog 3-[(123)I]iodo-alpha-methyl-L-tyrosine (IMT) is under clinical evaluation as a SPECT tracer of amino acid transport in brain tumors. This study investigated the carrier systems involved in IMT transport in human glioma cells in comparison with [3H-methyl]-L-methionine (3H-MET). METHODS: Human glioma cells, type 86HG-39, were cultured and incubated for 1 min at 37 degrees C with IMT and 3H-MET in the lag phase (1.2 d after seeding), exponential growth phase (3 d after seeding), and plateau phase (8 d after seeding). Experiments were performed in the presence and absence of Na+, during inhibition of system L amino acid transport by 2-aminobicyclo[2.2.1 ]heptane-2-carboxylic acid (BCH), and during inhibition of system A amino acid transport by 2-(methylamino)-isobutyric acid (MeAIB). RESULTS: IMT and 3H-MET uptake decreased by 55%-73% when the cells entered from the exponential growth phase into the plateau phase (P< 0.05; n = 3-11). Inhibition by BCH reduced uptake of IMT in the lag phase, exponential growth phase, and plateau phase by 90%-98% (P < 0.001; n = 3-6) and the uptake of 3H-MET by 73%-83% (P < 0.001; n = 3-11). In a Na+-free medium 3H-MET uptake was reduced by 23%-33% (P < 0.05; n = 3-11), whereas IMT uptake was not significantly different. MeAIB showed no significant effect on IMT or 3H-MET uptake in either phase. CONCLUSION: Transport of both IMT and 3H-MET depends on the proliferation rate of human glioma cells in vitro and is dominated by BCH-sensitive transport. These data indicate that system L is induced in rapidly proliferating glioma cells and is the main contributor to the uptake of both tracers. 3H-MET transport showed a minor Na+ dependency that was not attributable to system A. The similarity of transport mechanisms of both tracers emphasizes the clinical equivalence of IMT SPECT and (11)C-MET PET for the diagnostic evaluation of gliomas.