23-羟基白桦酸的碘标记及其在荷肝癌HepA肿瘤鼠体内的分布

采用双氧水法对23-羟基白桦酸进行131I标记;以硅胶纸为支持介质,V=氧甲烷∶V甲醇=9∶1为展开剂,测定标记率及标记物放化纯;ICR小鼠和荷肝癌HepA肿瘤鼠尾静脉注射131I-23-羟基白桦酸(0.74 MBq/只)后考察标记物的药代动力学性质及荷瘤鼠体内分布.结果显示,131I-23-羟基白桦酸标记率达98%,其放化纯在1、4、8 d分别为98.5%、97.3%、95.8%.131I-23-羟基白桦酸在正常小鼠体内血液清除较快,其药代动力学模型符合二室模型.注射后0.5 h荷肝癌HepA肿瘤鼠肝摄取最高(9.14%ID·g-1组织),其次为肾、血、脾、肠、肺、肿瘤,脑中分布最少,仅为0.28%ID·g-1组织;肿瘤/肌肉比值＞3.表明碘标23-羟基白桦酸标记率高,标记物稳定;碘标记物在荷肝癌HepA肿瘤鼠中的肿瘤靶向摄取提高2倍,可能是一新型增效的核素靶向治疗药物.     

藤黄酸的标记及其小鼠体内分布实验

通过¹³¹I 标记藤黄酸以分析其在肿瘤细胞中的摄取及动物体内的分布。采用双氧水标记、氯仿萃取,以聚酰胺薄膜为支持介质、氯仿 甲醇(体积比为40∶1）为展开剂,测定标记率及放化纯;分析肿瘤细胞MCF-7对¹³¹I-藤黄酸的摄取;KM小鼠尾静脉注射¹³¹I-藤黄酸（每只185 kBq）,于不同时间处死,取各脏器,称重、测量计数率,计算每克组织百分注射剂量率。¹³¹I-藤黄酸标记率达86%,放化纯在1, 4, 20 d分别为97.2%,95.4%,93.3%; MCF-7在30 min时对¹³¹I-藤黄酸摄取率达3.50%,显著高于对Na¹³¹I的摄取（P<0.01）;¹³¹I-藤黄酸在体内分布广泛,以肝、肾和肠为最多,肝中5 min时放射性摄取达25.93%ID/g, 4 h则为5.54%ID/g,而肾中5 min时为6.37%ID/g, 4 h时为2.46%ID/g;甲状腺中的放射性摄取随时间的延长而增加。¹³¹I-藤黄酸标记物稳定;肿瘤细胞MCF-7对¹³¹I-藤黄酸有显著摄取;体内主要通过肝肾代谢。     

碘标锰卟啉及其小鼠体内分布

通过131I标记锰卟啉(MnTBAP)探讨锰卟啉在小鼠体内的分布代谢。采用Iodogen法对锰卟啉进行131I标记;以聚酰胺薄膜为支持介质、生理盐水为展开剂,测定标记物的标记率和放化纯度;KM小鼠尾静脉注射131I-MnTBAP(每只185kBq,n=6),分别于注射后5、10、30、60、120、240、1 440min取各脏器,称重、测定计数率,计算每克组织摄取注射剂量的百分率(%ID/g)。结果表明,131I-MnTBAP标记率达96.3%,其放化纯在标记后2、24、48h分别为96%、95%、94.5%;动物实验显示131I-MnTBAP在小鼠体内广泛分布,主要经肝和肾脏进行代谢,肝、肾的放射性摄取在注入后5min时分别为8.34%ID/g、12.23%ID/g,4h时则分别下降为0.34%ID/g、0.73%ID/g,血液中放射性清除较快,注入后5min时血液中放射性摄取为5.55%ID/g,4h为0.86%ID/g。因此,碘标记锰卟啉的标记物体外稳定,体内主要经肝、肾代谢,可用于进一步的微量示踪研究。     

碘标延胡索乙素及其小鼠体内分布

本文通过131I标记延胡索乙素(THP)以探讨其在小鼠体内的分布代谢.采用氯胺-T法对THP进行131I标记;以三氯甲烷萃取,聚酰胺薄膜为介质、正己烷:三氯甲烷:甲醇:醋酸=2:3:0.5:0.055(V/V)为展开剂,测定标记物的标记率和放化纯;KM小鼠尾静脉注射131I-延胡索乙素(185 kBq/只,n=6),分别于注射后5、10、30、60、120、240、1440 mim取各脏器、及脑部额叶、顶叶、枕叶、海马、纹状体、丘脑和血,称重、计数,计算每克组织百分注射剂量率(%ID·g-1),结果表明,131I-延胡索乙素标记率达76%,纯化后其放化纯为97.3%,7和20天后分别为95.4%、96.8%;动物实验显示131I-延胡索乙素在小鼠体内广泛分布,主要经肝和肾进行代谢,5min时%ID·g-1分别为14.35、6.55,脂肪和肠也有较高分布,5min时ID·g-1分别为3.05、3.91;脑组织中5-10min即达峰值,各脑区均有分布,其中以顶叶、额叶和小脑略高,2h后脑中基本代谢完毕.由此可见,碘标延胡索乙素标记物稳定,体内主要经肝肾代谢,脂肪及脑内各区域也有较高分布,可用于进一步的微量示踪研究.     

碘标白藜芦醇及其小鼠体内分布

通过碘¹³¹标记白藜芦醇探讨白藜芦醇在小鼠体内的分布代谢。采用过氧化物酶法对白藜芦醇进行¹³¹I标记;经乙酸乙酯萃取纯化,以聚酰胺薄膜为支持介质,V(三氯甲烷)∶V(丙酮)∶V(乙醇)∶V(水)=4∶4∶0.5∶0.4为展开剂,测定标记物的标记率和放化纯;KM小鼠尾静脉注射¹³¹I白藜芦醇（每只0.185MBq,n=5）。¹³¹I白藜芦醇标记率达69.3%,萃取分离后其放化纯为959%,3、7和15d后分别为92.0%、90.4%、90.1%;动物实验显示,¹³¹I白藜芦醇在小鼠体内广泛分布,主要经肝和肾进行代谢,5min时每克组织百分注射剂量率(%ID•g^-1)分别为16.35、13.05,在肠中也有较高分布,10min时%ID•g^-1为11.70;甲状腺的摄取率随时间的延长而增加。碘标白藜芦醇标记物较稳定,可用于进一步的微量示踪研究。     

β-CIT的131I标记及其初步临床应用

用过氧乙酸法进行了β-CIT的131I标记,并用标记物对4例正常对照、8例帕金森氏病(PD)患者、3例帕金森氏综合征(PS)患者进行显像,计算纹状体与小脑的放射性摄取比(特异性摄取)及纹状体131I-β-CIT摄取的非对称指数AI.结果显示131I-β-CIT放化纯度达(97.6±0.3)%,室温下放置4 h以及分别与水、人新鲜血清孵育4 h后,其放化纯度仍均＞95%;纹状体能特异摄取131I-β-CIT,与正常对照组及PS组相比,PD患者双侧纹状体摄取的放射性明显降低(P＜0.01),且症状对侧降低更明显;PS患者与正常对照组相比,其纹状体摄取无明显差异(P＞0.05).直线回归分析显示,PD患者症状的严重程度与纹状体特异摄取131I-β-CIT下降密切相关.提示131I-β-CIT多巴胺转运蛋白显像可作为PD诊断、鉴别诊断和病情严重程度的客观指标.     

碘标记毒死蜱及其在小鼠体内的生物分布

为探讨¹³¹I标记毒死蜱（Chlorpyrifos, CPF）在小鼠体内的分布特点,采用Iodogen法对CPF进行¹³¹I标记,KM小鼠尾静脉注射¹³¹I-CPF（185 kBq/只,n=5）,分别于注射后5、10、30、60、120、240、1440 min取各脏器,计算每克组织摄取注射剂量的百分率（%ID/g）。结果显示,¹³¹I-CPF标记率达93.5%,放化纯度为96.9%,¹³¹I-CPF在小鼠体内广泛分布,主要经肺、胃、小肠、大肠、肌肉和颌下腺吸收,其放射性摄取率在注药后 10 min 时达高峰,分别为37.12%ID/g、6.18%ID/g、8.12%ID/g、8.15%ID/g、7.04%ID/g和7.02%ID/g;经肝和肾进行代谢,其放射性摄取率在5 min时分别为4.34%ID/g和8.50%ID/g, 4 h为0.22%ID/g和 0.69%ID/g。血液中放射性清除较快,放射性摄取率在注入后5 min时为37.27%ID/g,4 h为1.35%ID/g。碘标记CPF体外稳定,体内主要经肺和消化道吸收,肝、肾代谢,可用于进一步的微量示踪研究。     

^131I标记肿瘤血管靶向多肽的实验研究

设计合成含精氨酸-精氨酸-亮氨酸（RRL）序列的多肽,并用氯胺-T法对其进行^131I标记,标记率约60％,放化纯度〉99％。体外放置24h放化纯度仍≥90％。肿瘤对^131I标记多肽的摄取在注射后明显高于其他器官,注药后24h,肿瘤对^131I-多肽的摄取约为0．65％ID／g,肿瘤与肌肉的放射性摄取比（T／NT）达9．08。以上结果表明：通过氯胺-T法对该多肽进行^131I标记是可行的,标记物可在体外稳定存放24h;^131I-多肽可以靶向肿瘤血管,有进一步研究的价值。     

3H11的~(123)I标记及其生物分布

采用Iodogen氧化法对胃癌单克隆抗体3 H11进行了123I标记,用PD-10层析柱分离纯化标记物,纸层析法测定标记物的标记率和放化纯度,评价标记物的体外稳定性,并观察了标记物在正常小鼠体内的生物分布。标记结果显示,123I-3 H11的优化标记条件为:Iodogen 10μg、3 H11 30μg、Na123I溶液20μL(13.3 MBq)、磷酸盐缓冲溶液100μL(pH7.4、0.2 mol/L)、常温下反应8 min,123I-3 H11标记率70%~80%;稳定性结果显示,标记物在4℃人血清中的体外稳定性较好,放置48 h后放化纯度92%;正常昆明鼠体内生物学分布显示,全抗3 H11血液半清除时间为12.25±0.25 h,胃组织有明显摄取。以上结果提示,123I-3 H11是一种很有前景的肿瘤放射免疫显像剂。     

~(123)Ⅰ-邻碘马尿酸的动物实验和临床初步应用

放射性核素标记的邻碘马尿酸是检查肾功能和肾血流量的放射性药物。标记邻碘马尿酸的放射性核素大多采用碘的同位素,常用的为~(131)I,也有用~(123)I标记。本文通过动物实验和放射自显影术了解~(123)I-邻碘马尿酸在动物体内和肾内的分布,并与~(131)I-邻碘马尿酸进行临床应用对比,以评价其优缺点。     

Radioiodine-Labeling of Chlorpyrifos and Its Biodistribution in Mice

To investigate the preparation of radioiodinated Chlorpyrifos and its biodistribution in mice, Chlorpyrifos was labeled with¹³¹I using the Iodogen method. Biodistribution studies were carried out in KM mice. At different times after radiopharmaceutical i.v. administration (185 kBq¹³¹I-Chlorpyrifos/mouse, n=5), the animals were sacrificed. Blood samples and the tissues of interested were collected, weighted and counted. The percentage of injected does per gram (%ID/g) was calculated for each sample. The labeling yield of ¹³¹I-Chlorpyrifos was 93.5%, The radiochemical purity (RCP) was 96.9%. Biodistribution in mice demonstrated that¹³¹I-Chlorpyrifos was extensive, and the uptakes mainly occur in lung, stomach, small-intestine, colon, musle, and submaxillay gland, as indicated by their amount of 37.12%ID/g, 6.18%ID/g, 8.12%ID/g, 8.15%ID/g, 7.04%ID/g, and 7.02%ID/g at 10 min, respectively. And it was metabolized in liver and kidney, as indicated by their uptake of 4.34%ID/g and 8.50%ID/g at 5 min, and 0.22%ID/g and 0.69%ID/g at 4 h, respectively. In addition,¹³¹I-Chlorpyrifos was cleared out from blood quickly, and the uptake of¹³¹I-Chlorpyrifos in blood was 37.27%ID/g at 5 min, and decreased to 1.35%ID/g at 4 h post injection. In conclusion, ¹³¹I-Chlorpyrifos was stable in vitro and it was absorbed in lung and digestive tract, and it was metabolized mainly in liver and kidney, worthy of further investigation to trace the compound in vivo and in vitro.     

125I-interleukin-8 radiolabelling and in vivo distribution

1 Introduction Interleukin-8(IL-8) is expressed as a 99 aminoacid protein by monocytes, endothelial cells, fibro-blasts and many cell types of epithelial origin. Fol-lowing cleavage of a signal peptide and further prote-olytic processing at the ami…     

Tumor angiogenesis imaging agent:biodistribution of 131I-YG5 and 131I-Boc-YG5

The cyclic peptide YG5 and the t-butyioxycarbonyl(Boc)-modified analog(Boc-YG5)were labeled with radioiodine.The radiochemical purity of 131I-YG5 or 131I-Boc-YG5 was almost 100% after purification by RP-HPLC.Biodistribution in BALB/C nude mice bearing MCF-7 tumor was measured.After t-butyloxycarbonyl(Boc)-modification,the 131I-Boc-YG5 was quite resistant to deiodination in vivo,resulting in negligible radioactivity accumulation in thyroid.The radiotracer clearance in tumor became faster,the absolute tumor uptake decreased for131I-Boc-YG5,but the tumor-to-tissue uptake ratios increased.The uptake ratios of tumor to muscle,blood,heart,and lung at 1 h post injection reached 4.73,1.70,4.09 and 1.70,respectively.It is demonstrated that Boc-group is an effective prosthetic one to prevent deiodination in vivo and improve tumor imaging for radioiodinated NGR.     

Pharmacological studies of dopamine transporter imaging agent 125／131I－β－CIT

To prepare ^125/131I-β-CIT(2β-carbomethoxy-3β-(4-iodophenyl)tropane) as an imaging agent for dopamine transporter (DAT),the labeling method from tributylstannyl precursor with peracetic acid has been reported in this article.The radiochemical purity(RCP) of the labeled compound was over 95% determined by HPLC and TLC.The stability,partition coefficients were also determined.The pharmacological studies of the imaging agent were performed in rats,mice,rabbits and normal monkey.The ligand showed preferable uptake in rats,mice,rabbits and normal monkey.The ligand showed preferable uptake in brain (1.9%ID/organ in rats and 4.5%ID/organ in mice at 5min).The ratios of striatum/cerebellum,hippocampus/cerebellum and cortex/cerebellum were 29.8,3.97and 4.75 at 6h in rats,and 8.52,2.99 and 3.06 at 6h in mice,respectively.In monkey brain imaging the ratios of striatum/frontal cortex(ST/FC)and striatum/occipital cortex(ST/OC) were 5.14 and 5.97 at 4h.respectively,All of above showed the high affinity of the ligand to DAT,The compound was primarily metabolized in liver because the hepatic uptake was much higher than other organs(75.4%ID/organ at 18h).The half-life of blood elimination was 5min.The dose received by mice was 2500 times as high as that received by human in the test of undue toxicity,which evaluated the safety of the agent.All the results suggest that β-CIT can be used as a potential DAT imaging agent.     

~（131）Ⅰ—MIBG比活度对鼠心肌交感神经囊泡内外摄取的影响

研究了两种比活度的１３１Ⅰ－ＭＩＢＧ在正常及利血平抑制后在鼠体内的分布，结果表明：注射后４ｈ，正常鼠心肌对３．２２ＴＢｑ／ｇ的ＭＩＢＧ摄取为９．０８％ＩＤ／ｇ，明显高于对１８．５ＧＢｑ／ｇ的摄取（４．８７％ＩＤ／ｇ）。计算表明，比活度主要影响了鼠心肌交感神经囊泡内摄取，而与囊泡外摄取无关．当ＭＩＢＧ用于心肌显像时，高比活度的ＭＩＢＧ有利于诊断。     

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.     

131I-epidepride的制备与SD大鼠体内分布特性研究

采用双氧水标记法和氯胺 -T法进行13 1I -epidepride标记 ,考察标记物的纯度及稳定性 ,并进行SD大鼠体内分布特性研究。实验结果表明 ,双氧水法和氯胺 -T法标记率分别为 97.4 %和 5 2 .9%。标记物的生理盐水溶液室温放置 4h ,放化纯大于 90 %。大鼠静脉注射13 1I -epide pride的生理盐水溶液后 ,纹状体与小脑比值在注射后 32 0min时高达 2 37:1。13 1I -epidepride进入血液后很快被组织摄取 ,其中以肺的早期摄取最高 (2 .11± 1.0 5 ) %ID·g- 1,各脏器的清除均较快 (T1/2 <4h) ,甲状腺的摄取率随时间的延长而增加。     

The Research onBiodistribution of 131I-Iodosennoside A in Normal Mice and toEvaluate Myocardial Activity

Purpose: The objective ofthis project is to evaluate biodistribution of [¹³¹I]Iodosennoside Ain normal mice and explore the feasibility on the diagnosis of myocardialinfarction. Methods: Iodogen method was used to radioiodinate sennoside A with¹³¹I.[¹³¹I]Iodosennoside A was intravenously injected into mice. Threegroups of mice were killed at 4 h, 24 h and 48 h post injection respectivelyand the radioactive uptake in major organs were calculated. Rats were subjectedto left anterior descending (LAD) coronary artery ligation to induce acutemyocardial infarction. Rat models of myocardial infarction were intravenouslyinjected [¹³¹I]iodosennoside A. 24 h after injection of [¹³¹I]iodosennosideA, the regional distribution of radioiodinated sennoside A was determined byradioactivity counting technique. 2,3,5-triphenyl tetrazolium chloride (TTC)staining and autoradiography were performed with 2 mm thick sections of heartsfor postmortem verifications. Results: The study showed high uptake of [¹³¹I]iodosennosideA in kidneys and fast blood clearance. At 24 h post injection, radioactivityconcentration in infarcted myocardium was over 11.9 times higher than in normalmyocardium. Preferential uptake of the [¹³¹I]iodosennoside A innecrotic tissue was confirmed by perfect match of images from TTC staining andautoradiography. Conclusion: The result proved that [¹³¹I]iodosennosideA has myocardial necrosis affinity and may serve as a marker on the diagnosisof myocardial infarction.