5-羟色胺受体显像剂18F-MPPF的合成和标记

报道了5-羟色胺(5—HTlA)受体显像剂4-[^18F]氟—N-[2-[1-(2-甲氧基苯基)-1—哌嗪基乙基]-N—2吡啶基-苯甲酰胺(^18F-fluor-N-[2-[1-(2-methoxyphenyl)]-1-PiPenninyl]ethyl—N-2-Pridinyl—benzaInide,^18F-MPPF)的合成和标记。标记前体MPPN02和各步合成中间体均由红外、元素分析、核磁共振和质谱确证;采用两种加热方法进行氟代亲核置换标记反应。结果显示,微波法标记的放化产额(34％—50％,n＝10)明显比油浴加热标记法(8％一24％,n＝10)高,反应时间(40-50min)也比油浴加热标记法(70—40min)短,用TLC和HPLC检测放射化学纯度(RCP)均大于95％,可用于临床前研究。     

两种125I标记的神经紧张肽类似物的动物体内分布

采用氯胺T法对神经紧张肽类似物NT1和NT2进行^125I标记,并观察了^125I-NT1和^125I-NT2在正常小鼠和荷人结肠癌裸鼠体内的分布.结果显示,^125I-NT1和^125I-NT2标记率分别为68%和76%,经Sep-Pak-C18反相柱分离后,放化纯度〉98%;两种125I标记的NT类似物血液清除较快,部分由肝、肾脏排泄,体内分布基本一致,对肿瘤具有相似的靶向性.这说明两种NT类似物N端Arg和Lys互换对其体内的分布特性没有明显影响.与^125I-NT1相比,^125I-NT2在体内的清除速度更快,在胃中更稳定,其T/NT也更高,更适于作进一步研究.     

Annexin V的125I标记及其在正常小鼠体内的分布

采用Iodogen法对Annexin V进行了^125I标记,并观察了其在正常小鼠体内的分布情况.标记结果显示,^125I-Annexin V 标记率达94.9%,纯化后放化纯度达99%;室温放置72 h后,放化纯度仍保持在92%以上,表明其体外稳定性较好.生物分布结果显示,^125I-Annexin V在肾脏中放射活性最高,其次为血液、肝脏、心、肺、脾;脑不吸收^125I-Annexin V;肌肉、骨骼组织摄取亦较少;各组织、器官放射性摄取在1 h内除血液下降稍慢外,其余均有明显下降.表明^125I-Annexin V 适合用作核医学诊断试剂.     

鸡烟碱样胆碱能受体与[~(125)I]-α-银环蛇毒素结合动力学的研究

从鸡脑及骨骼肌中分离提取烟碱样胆碱能受体,用[~(125)I]-α一银环蛇毒素进行受体-配体结合动力学研究。结果表明,这种结合呈二级动力学反应性质。脑视叶中提纯的受体和骨骼肌中分离的受体,K_D值分别为129pM及4pM(25℃)。烟碱、箭毒碱等可抑制受体-配体的结合反应并测得各自的抑制常数及Hill系数。     

细胞凋亡显像剂[18F]FEDPA的合成和标记

为制备新型细胞凋亡显像剂[18F] FEDPA,合成了前体(2-{2-[2-(3,5-二-N,N-二(2-甲基吡啶)氨甲基-苯氧基)乙氧基]-乙-基}乙基)-胺-总收率5％(以化合物4计).后经过18F标记合成[18F] FEDPA,标记率(8.9士0.3)％(经校正,n=2),HPLC检测其放射化学纯度为77％.     

Annexin V的~(125)I标记及其在正常小鼠体内的分布

采用Iodogen法对Annexin V进行了125I标记,并观察了其在正常小鼠体内的分布情况。标记结果显示,125I-Annexin V标记率达94.9%,纯化后放化纯度达99%;室温放置72 h后,放化纯度仍保持在92%以上,表明其体外稳定性较好。生物分布结果显示,125I-Annexin V在肾脏中放射活性最高,其次为血液、肝脏、心、肺、脾;脑不吸收125I-Annexin V;肌肉、骨骼组织摄取亦较少;各组织、器官放射性摄取在1 h内除血液下降稍慢外,其余均有明显下降。表明125I-Annexin V适合用作核医学诊断试剂。     

125I标记苯并噻唑类A β斑块显像剂的合成及生物分布

为了研制123I标记的、诊断阿尔茨海默病的苯并噻唑类A β斑块显像剂,合成了4个125I标记的苯并噻唑类衍生物,放射化学纯度大于95%.动物体内分布实验表明,3′-125I-BTA,3′-125I-CBTA,3′-125I-BTA-Ac和3′-125I-CBTA-Ac在小鼠脑中有较高的初始摄取,给药后2 min的脑摄取量分别为:10.28,3.62,3.33和3.71 %/g;3′-125I-BTA,3′-125I-BTA-Ac和3′-125I-CBTA-Ac脑清除较快,2 min与6 min的脑摄取量之比分别为:7.3,6.2和5.7.研究结果表明,3′-123I-BTA是一个很有发展潜力的A β斑块SPECT显像剂.     

多巴胺D2受体显像剂^125I—IBZM的合成与标记

合成了标记前体Ｓ－（－）－２－羟基－６－甲氧基－Ｎ－［（１－乙基－２－吡咯烷基）甲基］苯甲酰胺（Ｓ－（－）－ＢＺＭ）。光谱数据与结构相符。以Ｓ－（－）－ＢＺＭ为前体，用１２５Ｉ－ＮａＩ标记，成功地制备了Ｓ－（－）－３－１２５Ｉ－２－羟基－６－甲氧基－Ｎ－［（１－乙基－２－吡咯烷基）甲基］苯甲酰胺（Ｓ－１２５Ｉ－ＩＢＺＭ）。标记率大于８０％，放射化学纯度大于９０％，整个制备过程仅需４５ｍｉｎ，利于药盒化生产。     

两种~(125)I标记的神经紧张肽类似物的动物体内分布

采用氯胺T法对神经紧张肽类似物NT1和NT2进行125I标记,并观察了125I-NT1和125I-NT2在正常小鼠和荷人结肠癌裸鼠体内的分布。结果显示,125I-NT1和125I-NT2标记率分别为68%和76%,经Sep-Pak-C18反相柱分离后,放化纯度>98%;两种125I标记的NT类似物血液清除较快,部分由肝、肾脏排泄,体内分布基本一致,对肿瘤具有相似的靶向性。这说明两种NT类似物N端Arg和Lys互换对其体内的分布特性没有明显影响。与125I-NT1相比,125I-NT2在体内的清除速度更快,在胃中更稳定,其T/NT也更高,更适于作进一步研究。     

N-琥珀酰亚胺3 -[125I]碘苯甲酸酯(S125IB) 的放射化学合成

利用Iodogen法成功地对N-琥珀酰亚胺 3-(三正丁基锡)苯甲酸酯(ATE)进行了放射性碘-125标记,利用Sep-Pak硅胶柱实现了干扰蛋白标记的ATE及Iodogen与S125IB的分离,得到了放射性碘间标蛋白质有用的中间体S125IB,标记率93%以上。并研究了影响标记的因素,得出较佳标记条件为:ATE与 Na125I摩尔比6:1、氧化剂 Iodogen用量7mg、室温反应5min。     

Synthesis of serotonin transporter imaging agent [^125I]ADAM

The synthesis of serotonin transporter imaging agent [^125I] -2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine(^125I] ADAM) was reported. The chemical structure of the labeling precursor 5- (tributylstannyl) -2-((2-((dimethylamino)methyl)phenyl)thio)phenylamine and all its intermediates were verified by IR, ^1HNMR and MS. The radioiodinated compound was prepared using iododestannylation reaction by hydrogen peroxide. Final radiochemical purity was above 95% determined by TLC.     

[~(125)I]TZDM的制备

优良的Aβ显像剂必须对Aβ斑块有较高的亲和性,而体外竞争结合实验是筛选Aβ斑块显像剂的有效方法,实验中需要使用放射性配基[125I]TZDM。以对溴苯胺为起始原料,经过四步反应合成了[125I]TZDM的前体化合物Bu3Sn-TZDM,并通过125I进行标记制备了[125I]TZDM,标记率为62.5%。粗产物通过HPLC分离后,获得放射化学纯度大于97%的[125I]TZDM,实际产率为25%。     

Synthesis, radiolabeling and animal studies of [^131I]MPPI： A 5-HT1A imaging agent

The synthesis and biological evaluation of serotonin （5-HT1A） imaging agent [^131I]- 4-iodo-N-{2-[4-（2-methoxyphenyl）-piperazin-l-yl]-ethyl}-N-pridin-2-yl-benzamide （[^131I]MPPI） are reported. The chemical structure of aimed compound and intermediates were confirmed by IR, ^1HNMR, and MS. Radiochemical purity was above 99% determined by TLC. Biodistribution of [^131I]MPPI in rats displayed high uptake in hippocampus and low uptake in cerebellum. The ratio of the uptake of [^131I]MPPI in hippocampus to that in cerebellum was 2.90 at 30 rain post injection. The radioactivity in thyroid was 0.069 and 0.128% ID/g organ at 5 min and 120 rain, respectively, and it was increased with time, which suggests that in vivo deiodination may be the major route of metabolism. Ex vivo autoradiography of brain section displayed significant decrease of radioactivity in hippocampus when pretreated with 8-OH-DPAT, a selective 5HT1A agonist, compared with control. These findings strongly suggested that ^131I-MPPI could be used as an in vivo marker for studies of pharmacology of the 5-HT1A receptor system in animals.     

Synthesis, radiolabeling and animal studies of [131I]MPPI: A 5-HT1A imaging agent

The synthesis and biological evaluation of serotonin (5-HT1A) imaging agent [131I]-4-iodo-N-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]-ethyl}-N-pridin-2-yl-benzamide ([131I]MPPI) are reported. The chemical structure of aimed compound and intermediates were confirmed by IR, 1HNMR, and MS. Radiochemical purity was above 99% determined by TLC. Biodistribution of [131I]MPPI in rats displayed high uptake in hippocampus and low uptake in cerebellum. The ratio of the uptake of [131I]MPPI in hippocampus to that in cerebellum was 2.90 at 30 min post injection. The radioactivity in thyroid was 0.069 and 0.128% ID/g organ at 5 min and 120 min,respectively, and it was increased with time, which suggests that in vivo deiodination may be the major route of metabolism. Ex vivo autoradiography of brain section displayed significant decrease of radioactivity in hippocampus when pretreated with 8-OH-DPAT, a selective 5HT1A agonist, compared with control. These findings strongly suggested that 131I-MPPI could be used as an in vivo marker for studies of pharmacology of the 5-HT1A receptor system in animals.     

Biological evaluation on 125I-ADAM as serotonin transporter ligand

ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine) is suggested as a promising serotonin transporter (SERT) imaging agent for central nervous system. In this paper, biodistribution studies in rats showed that the initial uptake of 131I-ADAM in the brain was high (1.087%ID at 2 min post-injection), and consistently displayed the highest binding (between 60~240 min post-injection) in hypothalamus, a region known with the highest density of SERT. The specific binding((T/CB)-1) of 131I-ADAM in hypothalamus were 2.94, 3.03 and 3.09 at 60, 120 and 240 min post-injection, respectively. The (T/CB)-1 was significantly blocked by pretreatment with paroxetine, which is known as a serotonin site reuptake inhibitor, while another nonselective competing drug (5HT2A antagonist) Ketanserin, showed no block effect. The rat brain autoradiography and analysis showed that there was a high 131I-ADAM uptake in hypothalamus, the ratio of hypothalamus/cerebellum was significantly reduced from 7.94±0.39 to 1.30±0.56 by pretreatment with paroxetine at 60 min post-injection. Blood clearance kinetics was performed in rats, and the initial half-life of 13.79 min and late half-life of 357.14 min were obtained. The kinetic equation is: C=3.6147e-0.0725t 1.0413e-0.0028t. The thyroid uptake was 0.009% ID and 1.421% ID at 2 min and 120 min post-injection, respectively, suggesting that in vivo deiodination may be the major route of metabolism. Toxicity trial showed that the dose per kilogram administered to mice was 1000 times greater than that to humans, assuming a weight of 50kg. These data suggest that 131I-ADAM may be useful for SPECT imaging of SERT binding sites in the brain.     

Synthesis, radiolabeling and animal studies of [~(131)I]MPPI: A 5-HTB_(1A) imaging agent

1 Introduction In the last two decades, considerable progress has been made in the understanding of the central nervous system (CNS) serotonin system. It is an important neurotransmission network that regulates various physiological functions and behavior, including anxi-ety and affective states.P[1-3]P The family of receptors activated by the neurotransmitter serotonin has been divided into at least seven classes (5-HTB1-7B), some of them further subdivided into different subtypesP[4, 5]P…     

一种烟碱乙酰胆碱受体(nAChRs)显像前体化合物的合成与125I标记研究

本文介绍一种可用于125/123I标记的A-85380类前体化合物--(S)-5-(三丁基锡烷基)-3-[[1-(叔丁氧基羰基)-2-甲氧基]氮杂环丁基]吡啶的设计、合成及125I标记研究.实验以2-糠胺和(S)-氮杂环丁基甲酸为起始物,先合成(S)-5-(三丁基锡烷基)-3-[[1-(叔丁氧基羰基)-2-氮杂环丁基]甲氧基]吡啶前体化合物,再用125I标记,制得5-[125I]I-A-85380.整个放射性标记的时间为50-55min,标记率大于30%.5-[125I]I-A-85380在室温下放置3天,其放化纯度仍在95%以上,表明其在体外具有较高的稳定性.     

Synthesis and biodistribution of [131I]IMPY

The synthesis and biodistribution of β-amyloid plaques imaging agent [^131I]-2- （4′-dimethylaminophenyl）-6-iodoimidazo[1,2-α] pyridine （[^131I]IMPY） were reported. The chemical structure of the labeling precursor 2-（4′-dimethylaminophenyl）-6- （tributylstannyl） imidazo[1, 2-α] pyridine and all its intermediates were verified by IR,HNMR and MS. The radioiodinated compound was prepared using iododestannylation reaction by hydrogen peroxide. Final radiochemical purity was above 95% determined by TLC. The in vivo biodistribution of [^131I]IMPY in normal mice showed excellent brain uptake and washout, indicating this thioflavin-T based small molecular probe has potential for in vivo imaging amyloid deposits.