n-Gluc-Lys([Al18F]NOTA)-TOCA的制备和初步生物学评价

    Preparation and Preliminary Biological Evaluation of n-Gluc-Lys([Al18F]NOTA)-TOCA

    • 摘要: 肿瘤细胞组织上常有一些生长抑素受体的过度表达,奥曲肽及其衍生物与生长抑素受体(SSTR)能够高特异性地结合,因此,应用18F标记的奥曲肽及其衍生物作为肿瘤示踪剂,可对生长抑素受体阳性肿瘤进行诊断和疗效评价。为开发一种能够高效快速合成的18F标记奥曲肽衍生物,用Al18F复合物和偶联了双功能螯合剂NOTA的糖基化奥曲肽衍生物n-Gluc-Lys(NOTA)-TOCA通过螯合反应制备了n-Gluc-Lys([Al18F]NOTA)-TOCA,放化反应合成时间为25~30min,标记率为69%,最终产品经HLB柱纯化后放化纯大于95%。标记物在体外稳定,水溶性高(lg P=-4.20±0.09(n=3))。正常鼠体内分布实验显示:标记物通过肾代谢;在肝中摄取很低,在生长抑素受体高表达的胰腺中有高摄取,血液和肌肉本底低。骨中的摄取低,说明标记物在体内无脱18F或Al18F的现象。本工作为进一步研究Al18F复合物标记的奥曲肽衍生物作为生长抑素受体阳性肿瘤显像剂提供了实验依据。

       

      Abstract: Octreotide and their derivatives can specificially bind with somatostatin receptor (SSTR) which is usually over-expressed on many tumor cells. So 18F labeled octreotide and their derivatives can be used for the diagnosis and evaluation of therapeutic efficacy of SSTR positive tumors. In order to explore a novel PET probe for diagnosis of SSTR positive tumors, the n-Gluc-Lys([Al18F]NOTA)-TOCA was radio-synthesized fast and efficiently using the chelation reaction of nGluc-Lys(NOTA)-TOCA with Al18F moiety. n-Gluc-Lys([Al18F]NOTA)-TOCA was a glycosylated octreotide derivative combined with 1,4,7-triazacyclononane-1,4,7-triacetic acid(NOTA). The labeling efficiency of n-Gluc-Lys([Al18F]NOTA)-TOCA is 69% and the total synthesis time is 25-30 min. The radiochemical purity is over 95% after HLB column purification. The stability in vitro is excellent, and the hydrophilicity is high(lg P =-4.20±0.09(n=3)). Biodistribution studies in normal mice at 2 h after injection show that the uptake of n-Gluc-Lys([Al18F]NOTA)-TOCA in kidney is high((13.83±3.52)%ID/g(n=5)) and the uptake in liver and bone is low. The uptake in samatostatin pancreas receptor express is high, and the background of blood and muscle is low. These preliminary results provide some experimental basis for further study of Al18F complex labeled octreotide and their analogues as tumor probes for the diagnosis of SSTR-positive tumors.

       

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