Uzgiris Egidijus
GE Global Research Center, Niskayuna, New York, USA.
Invest Radiol. 2004 Mar;39(3):131-7. doi: 10.1097/01.rli.0000107495.48025.97.
We wanted to test the hypothesis that linear extended polymers are able to translocate across compromised endothelia to a much higher degree than polymers that are in a coiled configuration. The basis for this hypothesis is the concept of polymer reptation, a process allowing linear polymers to move around fixed obstacles and through small pores.
The conjugation of polylysine with DTPA was varied from 55% to 95% of lysine moieties for a fixed polymer degree of polymerization. The variable conjugation constructs were assessed in their ability to enhance tumor signals in an animal model. The blood circulation time was also assessed, as was the proton relaxivity of the constructs.
The relaxivity values of the variable conjugation constructs indicated that the conformation of the highly conjugated polymers was consistent with an extended conformation. Images of the highly conjugated constructs with cryoelectron microscopy showed structures also consistent with an extended peptide chain conformation. These constructs gave tumor signal enhancements 10 times larger than observed for constructs of lower conjugation at the same injection dose.
The conformation of polymer agents is of decisive importance in the imaging efficacy of tumors. Polylysine conjugates of Gd-DTPA, at conjugation levels of 90% or higher, assume an extended linear conformation, which enables them to translocate across tumor endothelium more effectively than less highly conjugated polymers.
我们想要验证这样一个假设，即线性延伸聚合物比呈卷曲构型的聚合物更能跨受损内皮细胞转运。该假设的依据是聚合物链爬行的概念，这是一个允许线性聚合物绕过固定障碍物并穿过小孔的过程。
对于固定的聚合度，聚赖氨酸与二乙三胺五乙酸（DTPA）的共轭比例从赖氨酸部分的55%变化到95%。评估了可变共轭构建体在动物模型中增强肿瘤信号的能力。还评估了血液循环时间以及构建体的质子弛豫率。
可变共轭构建体的弛豫率值表明，高度共轭聚合物的构象与延伸构象一致。用冷冻电子显微镜观察高度共轭构建体的图像显示，其结构也与延伸肽链构象一致。在相同注射剂量下，这些构建体使肿瘤信号增强的程度比低共轭构建体大10倍。
聚合物制剂的构象对肿瘤成像效果至关重要。钆 - 二乙三胺五乙酸（Gd - DTPA）的聚赖氨酸共轭物在共轭水平达到90%或更高时呈延伸线性构象，这使其比共轭程度较低的聚合物更能有效地跨肿瘤内皮细胞转运。
