具有偵測細胞內銅金屬離子之螢光及磁振造影對比劑

Abstract

過去幾年來，由於磁振造影(MRI)之優點有(1)具有非侵入性(2)高解析度(3)不具有輻射之優點，使磁振造影成為臨床醫療診斷上相當重要之影像工具。且磁振造影之對比劑也愈來愈被重視，各種不同功能之對比劑也漸漸被開發。在本研究中，我們設計並合成由色氨酸衍生物之可偵測細胞中二價銅離子之磁振造影對比劑[Gd(Try-TTDA)]2-。[Gd(Try-TTDA)]2- 對銅離子之選擇性高於其他之金屬離子(Cu(II)> Fe(II)> Na(I)∼Ca(II)∼Mg(II)∼Zn(II) ∼La(III))，並且在銅離子存在下可消去[Gd(Try-TTDA)]2-上indole結構之螢光與改變內層水分子數而增加其弛緩率，且在ex-vitro 與 in vitro MR imaging之研究，也能佐證上述弛緩率之論點。由結果顯示[Gd(Try-TTDA)]2-相當具有潛力可成為利用螢光光譜儀與磁振造影來偵測二價銅離子之雙功能磁振造影對比劑。

Over the past few decades, increasing attention has been paid to synthesize contrast agent for magnetic resonance imaging (MRI). MRI is a non-invasive and high resolution technique that has become a powerful diagnostic tool in medicine. In this study, we designed and synthesized a tryptophan based contrast agent (4S)-4-indolyl-3,6,10-tri(carboxymethyl) -3,6,10-triazadodecanedioic acid (Try-TTDA) and its Gd(III) chelate ([Gd(Try-TTDA)]2□) that can recognize Cu2+ ion in the living cells. Moreover, the Gd3+ complex attributes excellent selectivity for Cu2+ over a choice of other metal ions. The interaction between Cu2+ and side chain indole of [Gd(Try-TTDA)]2□ was quenching of intrinsic tryptophan fluorescence. A gradual increases in the relaxivity and signal enhancement of ex-vitro and in vitro MR imaging upon Cu2+ detection. These results implicate that a new MR based contrast agent can serve as a Cu2+ sensor using fluorescence spectrophotometer and MR imaging.