点击化学法制备奥曲肽类似物^(18)F-Ta-Gluc-TOCA及其生物学评价

Preparation of ^(18)F Labeled Octreotide Derivatives ^(18)F-Ta-Gluc-TOCA by Click Chemistry and its Biological Evaluation

通过点击化学方法快速、方便合成18 F标记糖基化奥曲肽衍生物(18 F-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2-18 F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18 F-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18 F-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,60min时达到(4.34±0.47)%ID/g,在120min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。

The preparation of 18F labeled peptides usually need many reaction steps, long time, harsh reaction conditions, which greatly limits the application of 18F labeled PET probe. Using click chemistry for the synthesis of 18F labeled peptides make the reaction con- ditions more reliable, efficient and selective. The reaction conditions are mild, low cost, and fast. The purpose of this research was to synthetize the glycosylated octreotide deriva- tive quickly and easily, to develop a method of 18F labeled peptides by click chemistry. We also discussed the exploration of the feasibility with 18F labeled glycosylated octreotide de- rivatives as a somatostatin receptor positive tumor probe. This work prepared 2-~ F-azide ethane precursor compounds by nucleophilic substitution and then labeled Pr-Gluc-TOCA by click chemistry, finally we got the product 18F-Ta-Gluc-TOCA by purification.