点击化学法制备奥曲肽类似物18F-Ta-Gluc-TOCA及其生物学评价

doi:10.7538/tws.2013.26.02.0091

摘要/Abstract

摘要：

通过点击化学方法快速、方便合成¹⁸F标记糖基化奥曲肽衍生物(¹⁸F-Ta-Gluc-TOCA)，探讨¹⁸F-Ta-Gluc-TOCA用作生长抑素受体阳性肿瘤显像的可能性。通过亲核取代制备2-¹⁸F叠氮乙烷前体化合物，与奥曲肽前体Pr-Gluc-TOCA进行点击化学反应，经分离纯化后得到¹⁸F-Ta-Gluc-TOCA。测定了标记物的体外稳定性和脂水分配系数，重点研究¹⁸F-Ta-Gluc-TOCA在正常小鼠以及荷瘤裸鼠体内分布。结果表明，¹⁸F-Ta-Gluc-TOCA放化纯度为91%，体外稳定性良好，脂水分配系数为－0.43±0.05。正常小鼠体内生物分布结果表明：¹⁸F-Ta-Gluc-TOCA在血液中清除较快，主要通过肝脏代谢，部分经肾脏代谢。荷瘤裸鼠体内分布实验表明：¹⁸F-Ta-Gluc-TOCA在肿瘤中摄取较高，60 min时达到（4.34±0.47）%ID/g，在120 min时仍有较高的摄取。上述结果表明，¹⁸F-Ta-Gluc-TOCA有望用于生长抑素受体阳性肿瘤PET显像。

关键词: ^{font-family: 'Times New Roman'">18}font-family: 'Times New Roman'">Ffont-family: 'Times New Roman'">, font-family: 宋体">点击化学font-family: 'Times New Roman'">, font-family: 宋体">奥曲肽类似物

Abstract:

The preparation of ¹⁸F labeled peptides usually needmany reaction steps, long time, harsh reaction conditions, which greatly limitsthe application of ¹⁸Flabeled PET probe. Using click chemistry for the synthesis of ¹⁸F labeled peptides make thereaction conditions more reliable, efficient and selective. The reactionconditions are mild, low cost, and fast. The purpose of this research was tosynthetize the glycosylated octreotide derivative quickly and easily, todevelop a method of ¹⁸Flabeled peptides by click chemistry. We also discussed the exploration of thefeasibility with ¹⁸Flabeled glycosylated octreotide derivatives as a somatostatin receptor positivetumor probe. This work prepared 2-¹⁸F-azide ethane precursor compounds by nucleophilic substitution and then labeledPr-Gluc-TOCA by click chemistry, finally we got the product ¹⁸F-Ta-Gluc-TOCA by purification.In addition, the in vitro stability and octanolwater partition coefficient of ¹⁸F-Ta-Gluc-TOCA were measured.The biodistribution studies of ¹⁸F-Ta-Gluc-TOCAin normal mice and tumor bearing nude mice were investigated. The radiochemicalpurity of ¹⁸F-Ta-Gluc-TOCAwas 91%. The vitro stability was good. The octanol-water partition coefficientwas -0.43±0.05.The results of biodistribution in normal mice showed rapid clearance fromblood, and excreted mainly through the hepatobiliary metabolism, and also throughthe renal metabolism. The results of the biodistribution in tumor bearing nudemice showed high uptake in the tumor (4.34±0.47%ID/g, 60 min). The findings suggest that ¹⁸F-Ta-Gluc-TOCA is a potentialradiotracer for PET imaging of somatostatin receptor positive tumors.

Key words: ^{font-family: 'Times New Roman'">18}font-family: 'Times New Roman'">Ffont-family: 'Times New Roman'">, click chemistry, octreotide derivatives

温凯;陈宝军;郭飞虎;梁积新;殷胤;陈大明;崔海平. 点击化学法制备奥曲肽类似物¹⁸F-Ta-Gluc-TOCA及其生物学评价[J]. 同位素, 2013, 26(2): 91-97.

WEN Kai;CHENBao-jun;GUO Fei-hu;LIANGJi-xin;YIN Yin;CHEN Da-ming;CUI Hai-ping. Preparation of ¹⁸F Labeled Octreotide Derivatives¹⁸F-Ta-Gluc-TOCA byClick Chemistry and its Biological Evaluation[J]. Journal of Isotopes, 2013, 26(2): 91-97.

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点击化学法制备奥曲肽类似物¹⁸F-Ta-Gluc-TOCA及其生物学评价

Preparation of ¹⁸F Labeled Octreotide Derivatives¹⁸F-Ta-Gluc-TOCA byClick Chemistry and its Biological Evaluation

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