碘-123-β-CIT制備及在巴金森氏癥診斷之動物研究

背景：巴金森氏症所表現之錐體外症狀乃在於腦中黑質體(substantia nigra)的多巴胺神經細胞退化而導致神經傳導物質多巴胺分泌不足，無法協調由乙醯膽鹼(acetylcholine)傳導物質之神經系統功能過盛，以致產生震顫、僵直及運動遲緩等現象。核子醫學利用cocaine類似結構的標幟藥物對多巴胺轉運體(dopamine transporter)造影來評估腦組織多巴胺神經細胞的退化情況，進而用於巴金森氏症的診斷。本研究探討國內研製碘-123標幟2β-carmethoxy-3β-(4-iodophenyl)tropane(β-CIT)以及在巴金森氏症動物的生體分佈研究。方法：碘-123-β-CIT以氧化性去錫碘化反應製備；以Sprague-Dawley品系雄性大白鼠研究其藥物動力學。11隻實驗組大白鼠以6-hydroxy dopamine(6-OHDA)破壞腦多巴胺神經细胞，作為巴全森氏症動物模型。另外9隻大白鼠以相同方式注射生理食鹽水做為控制組。四週後，確認實驗組大白鼠多巴胺系統被破壞後，自大白鼠尾部靜脈注射0.5～1 mCi碘-123-β-CIT，在30分鐘、1小時、4小時之後，取得腦紋狀體、血液、肝、肺、腎、脾、睪丸、肌肉、骨骼等，精確稱重後，置於樣品瓶，以加馬計數器測量其放射活度，藉以計算各器官的劑量分佈。結果：碘-123-β-CIT在實驗組與控制組大白鼠之血液、肝、肺、腎、脾、睪丸、肌肉、骨骼之放射性劑量分佈相似。正常控制組左、右兩側紋狀體(striatum)之碘-123-β-CIT攝取量隨時間遞增，4小時之測量值最高。實驗組沒有注射6-OHDA的右側紋狀體，攝取情形與上述正常組類似；注射6-OHDA之左側紋狀體，碘-123-β-CIT於1小時即達最高值，但總攝取値較右側為低。結論：利用6-OHDA誘發巴金森氏症大白鼠模型，證實國內製備的碘-123-β-CIT可用於巴金森氏症之紋狀體多巴胺轉運體診斷造影。

關鍵字

碘-123-β-CIT ；巴金森氏癥大白鼠模型；生體分布

並列摘要

Backgrounds: Extrapyramidal symptoms/signs of Parkinson's disease(PD)are due to the lack of dopamine excreted from dopaminergic system of substantia nigra. Hyperactivity of cholinergic system in PD is characterized clinically by bradykinesia, tremor, and rigidity. In PD, impaired function of the nigrostriatal dopaminergic system due to neuronal degeneration is implicated in changes in the dopamine transporters which can be evaluated by nuclear imaging with radiolabeled cocaine analogues. We reported the pharmacokinetic study of domestically prepared 123I-β-CIT on parkinsonian rat model.Methods:123I-β-CIT was prepared in INER by an oxidative destannylation reaction. Animal models of PD including eleven rats were produced by the unilateral intrastriatal injections of 6-hydroxydopamine(6-OHDA)(experimental group).In the control group, nine rats were unilaterally intrastriatally injected normal saline. Samples of lung, liver, spleen, testis, muscle, bone and bilateral striatum were taken and weighed carefully. In addition, one-ml sample of blood was drawn from the heart immediately after sacrifice. Tissue concentration was calculated and expressed aspercent injected dose per gm(% ID/gm).Results: The results revealed that the radioactivity distribution of the blood, lung, liver, spleen, testis, muscle and bone were similar between control and experimental groups. The uptake of 123I-β-CIT in striatum of normal control increased with time, and the peak level of uptake was found at 4 hours after injection. Decreased 123I-β-CIT radioactivity was noted in the striatal area of intrastriatal injections of(6-OHDA),comparing with normal striatal side of experimental group and bilateral striatum of control group. Conclusions: With 6-OHDA-induced parkinsonian rat model, we proved that the domestically prepared 123I-β-CITcan be used for striatal dopamine transporter imaging study of Parkinson's disease.

並列關鍵字

123I-β-CIT ； parkinsonian rat model ； biodistribution

國際替代計量

碘-123-β-CIT制備及在巴金森氏癥診斷之動物研究

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