Micro-PET Imaging of αvβ3-Integrin Expression with 18F-Labeled Dimeric RGD Peptide
Micro-PET Imaging of αvβ3-Integrin Expression with 18F-Labeled Dimeric RGD Peptide
复制标题
DOI：
10.1162/1535350041464892
复制
发表时间：
2004-04-01
影响因子：
2.8
通讯作者：
Conti, Peter S.
中科院分区：
文献类型：
--
作者：
Chen, Xiaoyuan;Tohme, Michel;Conti, Peter S.
α(v)整合素作为细胞黏附分子，与肿瘤侵袭和血管生成密切相关。特别是α(v)β(3)整合素，其在增殖的内皮细胞和肿瘤细胞上特异性表达，是开发放射性示踪方法以评估血管生成和抗血管生成治疗的合理靶点。在本研究中，通过将一个4 - [F - 18]氟苯甲酰基部分连接到谷氨酸的氨基上，用F - 18（半衰期 = 109.7分钟）标记二聚环RGD肽E[c(RGDyK)](2)。所得到的[F - 18]FB - E[c(RGDyK)](2)具有高比活度（合成结束时为200 - 250 GBq/μmol），被给予皮下U87MG胶质母细胞瘤异种移植模型，用于微型正电子发射断层扫描（micro - PET）和放射自显影成像以及直接组织取样，以评估这种正电子发射断层扫描（PET）示踪剂的肿瘤靶向效能和体内动力学。与单体RGD肽类似物[F - 18]FB - c(RGDyK)相比，二聚RGD肽显示出明显更高的肿瘤摄取和更长的肿瘤滞留时间。二聚RGD肽主要通过肾脏排泄，而单体类似物主要通过胆汁途径排泄。注射二聚RGD肽1小时后的微型正电子发射断层扫描成像显示肿瘤与对侧背景的比值为9.5 ± 0.8。多价性的协同效应和改善的药代动力学可能是[F - 18]FB - E[c(RGDyK)](2)具有优越成像特性的原因。《分子成像》（2004年），3卷，96 - 104页。
The alpha(v) integrins, which act as cell adhesion molecules, are closely involved with tumor invasion and angiogenesis. In particular, alpha(v)beta(3) integrin, which is specifically expressed on proliferating endothelial cells and tumor cells, is a logical target for development of a radiotracer method to assess angiogenesis and anti-angiogenic therapy. In this study, a dimeric cyclic RGD peptide E[c(RGDyK)](2) was labeled with F-18 (t(1/2) = 109.7 min) by using a prosthetic 4-[F-18] fluorobenzoyl moiety to the amino group of the glutamate. The resulting [F-18]FB-E[c(RGDyK)](2), with high specific activity (200-250 GBq/mu mol at the end of synthesis), was administered to subcutaneous U87MG glioblastoma xenograft models for micro-PET and autoradiographic imaging as well as direct tissue sampling to assess tumor targeting efficacy and in vivo kinetics of this PET tracer. The dimeric RGD peptide demonstrated significantly higher tumor uptake and prolonged tumor retention in comparison with a monomeric RGD peptide analog [F-18]FB-c(RGDyK). The dimeric RGD peptide had predominant renal excretion, whereas the monomeric analog was excreted primarily through the biliary route. Micro-PET imaging 1 hr after injection of the dimeric RGD peptide exhibited tumor to contralateral background ratio of 9.5 +/- 0.8. The synergistic effect of polyvalency and improved pharmacokinetics may be responsible for the superior imaging characteristics of [F-18]FB-E[c(RGDyK)](2). Mol Imaging (2004) 3, 96-104.