腫瘤目標化磁振造影對比劑[Gd(DOTA-iRGD)]之合成及特性探討

Abstract

磁振造影對比劑與具有目標化功能的胜肽結合能用來區別一般組織與癌症病灶，藉由與目標細胞的結合而可以提升癌組織在磁振造影時的對比；iRGD是一段由9個胺基酸所組成的胜肽，具有將物質攜帶至αv integrin過量表現之癌細胞或組織新生血管，並且被細胞吞噬的能力。在這個研究中設計合成了攜帶iRGD胜肽的對比劑[Gd(DOTA-iRGD)]，希望藉由其被細胞吞噬的功能來更加提升磁振造影的對比，並對其進行物性、化性探討。[Gd(DOTA-iRGD)]在20 MHz、37.0 ± 0.1 ℃下，求得其弛緩率（r1）為4.91 ± 0.3 mM-1s-1；在細胞毒性方面，[Gd (DOTA-iRGD)]對於高度表現αv integrin的PC¬-3腫瘤細胞株會誘發凋亡的現象，但是對於低度表現的HT-1080細胞株在高濃度劑量時仍然沒有顯著的影響；由體外(in vitro) MRI結果顯示，比起低度表現αv integrin的HT- 1080細胞株，[Gd (DOTA-iRGD)]對於PC¬-3腫瘤細胞株能提升較高的對比顯影。

The MRI contrast agents bearing peptides as target moiety can be used to differentiate tumor tissue with normal one, the contrast of MR imaging will evaluate by specific binding to tumor tissue. iRGD is a cyclic peptide sequence compose of nine amino acid , with ability of brining material to αv integrin over expression or angiogenic endothelial cells and be uptake by cell. iRGD bearing MR contrast agent [Gd(DOTA-iRGD)] is designed and synthesized, expect it will evaluate the contrast of MR imaging by cell internalize and discuss it chemical and physical property. Relaxivity (r1) of [Gd(DOTA- iRGD)] under 20 MHz, 37.0 ± 0.1 ℃ is 4.91 ± 0.03 mM-1s-1. In cytotoxicity assay, [Gd(DOTA-iRGD)] induce apoptosis of PC-3, an αv integrin over expression cell line, but has no significant effect to lower expression HT-1080 cell line even at high concentration. In vitro MR imaging show that PC-3 cell line can evaluate more contrast than αv integrin lower expression HT-1080 cell line.