DO3A-betaG配位子及其鑭系金屬錯合物之合成、物性及化性之研究

本研究主要以合成出大環多胺基羧酸基的配位子DO3A-betaG及模擬其切割後之大環配位子HE-DO3A，並探討釓金屬錯合物與尿甘酸醛醣酵素在一定時間作用時，由HPLC結果得知，[Gd(DO3A-betaG)]在酵素作用時，6小時內即有明顯酵素切割表現。進而探討內層水分子數的變化，分別利用17O-NMR化學位移之變化及量測化學螢光半生期的方法，求出[Gd(DO3A-betaG)]與[Gd(HE-DO3A)]內層水分子數(q)變化由q=0.49改變成1.46，明顯增加一個內層水分子。由尿甘酸醛醣酵素存在時對釓金屬錯合物弛緩時間(T1)影響的研究發現，當酵素存在時，釓金屬錯合物由於酵素切割了尿甘酸醛醣基，使得內層水分子增加，而使得在弛緩時間的變化量於切割前後下降約25%。利用17O-NMR求得動力學參數而言，得[Gd(DO3A-betaG)]水交換速率(kex298)值為52.3?e106 s?{1，較[Gd(TTDA)]2?{及[Gd(TTDA-beta-GP)]2?{來得低，但比[Gd(DOTA)]?{及[Gd(DTPA)]2?{來得高；其分子轉動相關時間(298?豩)值為173 ps，則與[Gd(TTDA-beta-GP)]2?{?n(298?豩=175 ps)近似。以上結果可證明[Gd(DO3A-betaG)]為具酵素可切割特性之磁振照影對比劑。

關鍵字

磁振照影；對比劑；尿甘酸醛醣酵素

並列摘要

In this study, a beta-glucuronic acid-containing ligand DO3A-betaG and a modified enzyme-cleaved ligand HE-DO3A, was designed, synthesized and characterized. [Gd(DO3A-betaG)] was incubated with beta-glucuronidase (betaG) and detected the enzyme-cleavage behavior of [Gd(DO3A-beta G)]. The betaG cleaved beta-glucuronic acid residue of [Gd(DO3A-betaG)] in 360 mins and detected by HPLC fluorescence detector. The number of inner-sphere water of [Gd(DO3A-betaG)] and [Gd(HE-DO3A)] was obtained, through the Dy3+-induced 17O water NMR shifts experiments and chemical-luminescence method. The number of inner sphere water is significantly increased from q=0.49 to 1.46. Relaximetric studies shows that the T1 value of [Gd(DO3A-betaG)]?ndecreases about 25% in the presence of betaG and proves that the q value of [Gd(DO3A-betaG)] increased in the presence of betaG. The 17O NMR experiments were conducted to estimate the water exchange rate kex298 and rotational correctional time 298?豩. The value of [Gd(DO3A-betaG)] is 52.3?e106 s?{1 and significantly higher than those of [Gd(DOTA)]?n?{ and [Gd(DTPA)]2?{?nbut slightly lower than those of [Gd(TTDA-beta-GP)]2?{?nand?n[Gd(TTDA)]2?{. The rotational correctional time value of [Gd(DO3A-FPG)] is 173 ps and similar to [Gd(TTDA-beta-GP)]2?{. [Gd(DO3A-betaG)] is potentially suitable as bio-activated MRI contrast agents.