^(188)Re标记小剂量奥曲肽方法学及其在小鼠体内分布的研究

Labeling method of a low dosage of octreotide with rhenium-188 and its biodistribution in normal mice

目的 建立188Re标记小剂量奥曲肽(octreotide)的方法,观察其在小鼠体内的生物学分布。方法 SnCl2 ·2H2 O的用量为5 0～160 0 μg ,奥曲肽的用量为10、2 0或3 0 μg ,乙酸缓冲液的pH值从4.0至6.0 ,反应体系的温度为室温、60、80或10 0℃,淋洗液体积从0 .0 5至0 .2 0ml ,测定标记物的标记率及其在体外的稳定性。将标记物经小鼠尾静脉注射,于0 .5、1、2、4、2 4h取血液及主要脏器测量其放射性计数率值。结果 188Re直接法标记小剂量奥曲肽的最佳条件:葡庚糖酸钠(0 .3mmol/L) 0 .1ml,SnCl2 ·2H2 O(16g/L) 0 .0 5ml,乙酸缓冲液(pH =5 ) 0 .1ml,奥曲肽(0 .1g/L)0 .1ml,通氮气震荡反应1h ,再加入新鲜188Re淋洗液0 .1ml,10 0℃水浴3 0min ,188Re 奥曲肽标记率可达到(95 .3±1.8) % ,室温下放置2 4h放化纯为(89.6±2 .5 ) %。188Re 奥曲肽在正常小鼠体内主要分布于肝脏、肾脏及肠道。结论 研究建立的188Re标记奥曲肽操作简便,标记率高,体外稳定性好,无需进一步纯化,奥曲肽用量较小,预期能提高靶向定位质量,188Re 奥曲肽在小鼠体内主要被肠道、肝脏、肾脏等器官摄取。

Objective To study the method for labeling a low dosage of octreotide with rhenium-188 and its biodistribution in normal mice.Methods The amount of stannous chloride changed from 50 to 1?600 μg,octreotide was 10,20 or 30 μg,pH value of acetate buffer from 4.0 to 6.0, the volume of rhenium-188 perrhenate from 0.05 to 0.20 ml,the reaction temperature from room temperature to 100 ℃.The labeling efficiency and the in vitro stability of 188 Re-octreotide were analyzed.SPECT scanning was carried out before mice were killed.The blood and major organs were taken out from those mice at 0.5 ,1,2,4,24 h after been injected 188 Re-octreotide through the tail veins,and the radioactivity count of those organs were measured.Results The optimal conditions for rhenium-188 labeling reaction were as follows:0.1 ml sodium glucoheptonate (0.3 mmol/L), 0.05 ml stannous chloride (16 g/L) was dissolved by 0.1 mol/L hydrochloric, 0.1 ml acetate buffer (pH=5) and 0.1 ml octreotide (0.1 g/L) were mixed at room temperature for 1 h with nitrogen atmosphere and continuous agitation. 0.1 ml fresh rhenium-188 perrhenate was added,water bathing 100 ℃ for 30 min.It was found that the labeling efficiency of 188 Re-octreotide was (95.3± 1.8)%. After it was cooled in room temperature,radiochemical purity was (89.6± 2.5)% at 24 h. 188 Re-octreotide was mainly distributed in lives,small bowels,large bowels and kidneys.Conclusion This method of labeling octreotide with rhenium-188 is convenient with satisfactory in vitro stability and labeling efficiency,and does not need further purification to the labeling radiopharmaceutical before administration.The distribution of radionuclide will be reduced in the non-target organs because of the low dosage of octreotide.The clearance of 188 Re-octreotide from blood is fast. 188 Re-octreotide was up taken highly by small and large bowels,kidneys and livers.