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目的制备同位素~(99)Tc~m标记血管活性肠肽受体(vasoactive intestinal peptide receptor,VIPR)结合肽TP1724(标记率>90%),鉴定其理化性质,并探讨其在正常动物体内的生物分布特点、示踪动力学及显像表现。方法制备G(D)AGG-Aba-VP2(TP1724);~(99)Tc~m间接标记TP1724(Sn Cl2·2H2O还原法),纸层析法测定标记率和比活度;稳定性实验(体外)、人血浆蛋白结合实验、半胱氨酸置换实验及脂/水分配实验等鉴定标记多肽的理化性质;35只正常小鼠分成7组,每只尾静脉注射3.7 MBq~(99)Tc~m-TP1724后于不同时间处死,收集9种组织器官并称取质量、分别测定各种组织器官的放射性,换算为%ID/g(每克组织百分注射剂量);9只健康家兔各静脉注射37 MBq~(99)Tc~m-TP1724后不同时间取血,测定血液放射性并换算为k Bq/L,经DAS 3.1.6软件处理判断最佳房室模型,并得出动力学参数;5只健康家兔分别静脉注射37 MBq~(99)Tc~m-TP1724,SPECT动态显像观察体内放射性分布变化。结果~(99)Tc~m-TP1724的标记率(96.57±0.71)%,比活度(25.52±0.29)TBq/mmol。室温下隔绝空气放置4 h,放化纯度为(93.64±2.25)%;Sephadex G-50柱层析示,~(99)Tc~m-TP1724血浆蛋白结合率约为6.61%;~(99)Tc~mTP1724与不同浓度半胱氨酸37℃温育1 h后,未结合~(99)Tc~m含量无明显变化;脂/水分配系数lg P为-(1.99±0.02)。~(99)Tc~m-TP1724在健康家兔体内的动力学符合权重为1的二室模型,分布半衰期t1/2α为(2.64±1.32)min,消除半衰期t1/2β为(78.36±13.38)min。体内生物分布和/或动态显像示:血液放射性清除迅速;颈部及胃区未见异常放射性聚集,脑部显示低放射性分布;放射性大部分通过肾脏排泄,少量经肝胆分泌。结论~(99)Tc~m-TP1724标记方法简便、标记率和比活度高、稳定性好、体内动力学性质优良。
OBJECTIVE To prepare the vasoactive intestinal peptide receptor (VIPR) binding peptide TP1724 (labeled rate> 90%) and to identify its physico-chemical properties and to explore its bioactivity in normal animals Distribution characteristics, tracer dynamics and imaging performance. Methods The labeling rate and specific activity of G (D) AGG-Aba-VP2 (TP1724), indirect labeling of ~ (99) Tc ~ m TP1724 (Sn Cl2 · 2H2O reduction method) In vitro), human plasma protein binding assay, cysteine exchange assay and lipid / water partitioning assay. The 35 normal mice were divided into 7 groups and injected with 3.7 MBq ~ (99) Tc ~ m-TP1724 were sacrificed at different times, collected nine kinds of tissues and organs and weighed, respectively, measured radioactivity in various tissues and organs, in% ID / g (per gram of tissue injected dose); 9 healthy rabbits After intravenous injection of 37 MBq 99 Tc m -TP1724, blood was collected at different times, blood radioactivity was measured and converted to k Bq / L, and the best atrioventricular model was determined by DAS 3.1.6 software and kinetic parameters ; 5 healthy rabbits were intravenously injected with 37 MBq 99 Tc m -TP1724, SPECT dynamic imaging observed in vivo radioactive distribution changes. Results The labeling rate of (99) Tc-m-TP1724 was (96.57 ± 0.71)% and the specific activity was (25.52 ± 0.29) TBq / mmol. The separation of air at room temperature for 4 h, the radiochemical purity was (93.64 ± 2.25)%; Sephadex G-50 column chromatography showed that the binding rate of ~ (99) Tc ~ m-TP1724 plasma protein was about 6.61% Tc ~ mTP1724 and different concentrations of cysteine incubated for 1 h at 37 ℃, unbound 99 Tc m content did not change significantly; lipid / water partition coefficient lg P - (1.99 ± 0.02). The kinetics of ~ (99) Tc ~ m-TP1724 in healthy rabbits accorded with a two-compartment model with a weight of 1. The distribution half-life t1 / 2α was (2.64 ± 1.32) min and the elimination half-life t1 / 2β was (78.36 ± 13.38) min. In vivo biodistribution and / or dynamic imaging showed: rapid radioactive clearance of blood; no abnormal radioactive aggregation in the neck and stomach area; low radioactivity distribution in the brain; most radioactivity excreted by the kidneys and a small amount by the hepatobiliary excretion. Conclusion ~ 99 Tc m-TP1724 labeling method is simple, high labeling rate and specific activity, good stability, good in vivo kinetics.