具有Dansyl結構的銅離子磁振造影對比劑之合成與特性研究

Abstract

在本研究中，我們設計合成出可偵測二價銅離子的雙功能磁振造影對比劑[Gd(DNS-DOTA)]。當銅離子存在時，釓金屬錯合物[Gd(DNS-DOTA)]的內層水分子數(q)會從0增加到1，使弛緩率(r1)由原本的4.65 mM-1s-1上升至5.86 mM-1s-1。在磁振造影影像實驗中，我們觀察到當銅離子存在時，其影像訊號強度是高於沒有銅離子存在的環境。在光學實驗中當加入二價銅離子時，釓金屬錯合物[Gd(DNS-DOTA)]結構上的dansy會與銅離子反應而削弱釓金屬錯合物螢光表現。而且，釓金屬錯合物[Gd(DNS-DOTA)]對二價銅離子(Cu2+)的選擇性優於其他金屬離子，在有其他金屬離子存在的條件下，[Gd(DNS-DOTA)]對二價銅離子的選擇性仍不受干擾。共聚焦掃描顯微鏡(Confocal)的影像實驗證明釓金屬錯合物[Gd(DNS-DOTA)]在細胞內的螢光表現會被二價銅離子所抑制。因此，釓金屬錯合物[Gd(DNS-DOTA)]是具有相當潛力可成為偵測二價銅離子的雙功能磁振造影對比劑。

In the present study, we designed and synthesized MR-optical imaging agent, [Gd(DNS-DOTA)], for the detection of the divalent copper ion(Cu2+). Luminescence lifetime measurement shows the number of inner-sphere water molecules (q) in [Gd(DNS-DOTA)] is zero. However, upon addition of Cu2+ to [Gd(DNS-DOTA)], the q value changes from 0 to 1. Consequently increase in the relaxivity of [Gd(DNS-DOTA)] was observed in the presence of Cu2+. Consistent to relaxometric study, magnetic resonance imaging (MRI) experiments display the increase in signal strength with the increase in the Cu2+ ion concentration. In addition, attenuation in the fluorescence intensity of [Gd(DNS-DOTA)] was observed on adding Cu2+ ion which substantiate that the coordination profile of [Gd(DNS-DOTA)] is alter in the presence of Cu2+ ion. High coordination preference of [Gd(DNS-DOTA)] for Cu2+ ion over other metal ion was observed under the same condition. Last but not least, confocal imaging experiment shows that the fluorescence intensity [Gd(DNS-DOTA)] suppressed on incubating with 3T3 cell pretreated with Cu2+. Therefore, [Gd(DNS-DOTA)] is a potential MR-optical imaging agent for the detection of intracellular Cu2+ ion with high specificity.