摘要
合成了N-巯基乙酰基-VGG(MAVGG)及经葡萄糖和半乳糖偶联的MAVGG(糖肽Glu-MAVGG和Gal-MAVGG),对其进行了99Tcm标记,测定了标记物在正辛醇与水中的分配系数Pow,并观察了3种标记物在荷S180小鼠体内的分布。结果显示,化学合成得到的糖肽经IR、NMR与MS验证与所设计的结构一致9。9Tcm的标记率和放化纯度均大于90%9。9Tcm-Glu-MAVGG,99Tcm-Gal-MAVGG和99Tcm-MAVGG的lgPow分别为-1.974、-2.128和-1.378,其T1/2α分别为24.3、37.1和46.3 min,T1/2β分别为221.5、158.4和198.4 min。注射后3 h99Tcm-Glu-MAVGG、99Tcm-Gal-MAVGG和99Tcm-MAVGG在肿瘤中的摄取率分别为1.46、1.55与0.67,肿瘤与肌肉的放射性摄取比(T/NT)分别为3.74、7.38与3.53。以上结果表明,经糖基修饰后,多肽的脂溶性降低,血液清除速率增大,肿瘤摄取率增高。三种标记物中,99Tcm-Gal-MA-VGG具有较大的血液清除率、较高的肿瘤摄取率与T/NT,提示其有可能作为肿瘤显像剂。
Glucose and galactose are conjugated to the N-mercaptoacetyl Val Gly Gly （MA VGG）. The glycopeptides and MAVGG are labeled with ^99Tc^m. The partition coefficients between octanol and water （Pow） are measured. Glycopeptides or MAVGG labeled with ^99Tc^m are injected into the mice bearing S180 tumors. 10μL blood samplesare withdrawn at different time points and the radioactivities are counted and calculated for the effective halflife （T1/2） using a bi-exponential fit. Biodistribution is measured at 3 h postinjection and the percentage of injected dose per gram （ ID%/g ） and the radio-uptake ratio of tumor to normal tissue （T/NT） are calculated. The assigned structures are confirmed on the basis of IR, NMR and MS. The ^99Tc^m labeling yield and radiochemical purity is more over 90%. The lgPow of ^99Tc^m-Glu-MAVGG, ^99Tc^m-Gal-MAVGG and ^99Tc^m-MAVGG are -1.974, - 2. 128 and -1.378, respectively. The T1/2α of the three labeled peptides are 24.3, 37.1, 46. 3 min and T1/2β are 221.5, 158.4 and 198.4 min, respectively. The tumor uptake after 3 h postinjection is 1.46, 1. 55 and 0. 67 for ^99Tc^m-Glu-MAVGG, ^99Tc^m-Gal-MAVGG and ^99Tc^m-MAVGG, respectively. Their T/NT for tumor over muscle are 3.74,7.38 and 3.53, respectively. The results demonstrate that after carbohydrate conjugate of peptides, the lipophilicity is decreased , the blood clearance is increased and the tumor uptake is enhanced. Among three labeled compounds, ^99Tc^m-Gal-MAVGG posseses faster blood clearance, higher tumor uptake and T/NT. It suggests the potential utility of ^99Tc^m-Gal-MAVGG as a suitable tumor imaging agent in the future.
出处
《同位素》
CAS
北大核心
2006年第1期12-16,39,共6页
Journal of Isotopes
