PET Imaging of Integrin Positive Tumors Using F Labeled Knottin Peptides.
PET Imaging of Integrin Positive Tumors Using F Labeled Knottin Peptides.
复制标题
DOI：
10.7150/thno/v01p0403
复制
发表时间：
2011
期刊：
影响因子：
12.4
通讯作者：
Cheng Z
中科院分区：
文献类型：
--
作者：
Liu S;Liu H;Ren G;Kimura RH;Cochran JR;Cheng Z
用途：胱氨酸结（结蛋白）肽，工程化结合与整合素受体的高亲和力，已显示出作为分子成像剂在活体对象的前景。本研究的目的是评估U87 MG胶质母细胞瘤模型中18F标记的结蛋白的肿瘤摄取和体内生物分布。操作步骤：使用固相肽合成合成工程化的结蛋白突变体2.5D和2.5F，并在体外折叠，然后用4-硝基苯基2- 18F-氟丙酸酯（18F-NFP）放射性标记。使用微PET和生物分布研究在携带U87 MG肿瘤异种移植物的裸鼠中评价所得探针18F-FP-2.5D和18F-FP-2.5F。结果：18F-FP-2.5D和18F-FP-2.5F的MicroPET成像研究表明，在U87 MG异种移植小鼠模型中肿瘤摄取较高。该探针显示出从血液和肾脏中的快速清除，从而导致良好的肿瘤与正常组织对比度。特异性研究证实，当与大量过量的肽模拟物c（RGDyK）作为阻断剂共注射时，18F-FP-2.5D和18F-FP-2.5F具有降低的肿瘤摄取。结论：与先前发表的18F-FB-2.5D相比，18F-FP-2.5D和18F-FP-2.5F显示胆囊摄取减少。18F-FP-2.5D和18F-FP-2.5F使得U87 MG肿瘤的整合素特异性PET成像具有良好的成像对比度。与18F-FP-2.5F相比，18F-FP-2.5D表现出更理想的药代动力学，因此具有更大的临床转化潜力。
Purpose: Cystine knot (knottin) peptides, engineered to bind with high affinity to integrin receptors, have shown promise as molecular imaging agents in living subjects. The aim of the current study was to evaluate tumor uptake and in vivo biodistribution of 18F-labeled knottins in a U87MG glioblastoma model. Procedures: Engineered knottin mutants 2.5D and 2.5F were synthesized using solid phase peptide synthesis and were folded in vitro, followed by radiolabeling with 4-nitrophenyl 2-18F-fluoropropionate (18F-NFP). The resulting probes, 18F-FP-2.5D and 18F-FP-2.5F, were evaluated in nude mice bearing U87MG tumor xenografts using microPET and biodistribution studies. Results: MicroPET imaging studies with 18F-FP-2.5D and 18F-FP-2.5F demonstrated high tumor uptake in U87MG xenograft mouse models. The probes exhibited rapid clearance from the blood and kidneys, thus leading to excellent tumor-to-normal tissue contrast. Specificity studies confirmed that 18F-FP-2.5D and 18F-FP-2.5F had reduced tumor uptake when co-injected with a large excess of the peptidomimetic c(RGDyK) as a blocking agent. Conclusions: 18F-FP-2.5D and 18F-FP-2.5F showed reduced gallbladder uptake compared with previously published 18F-FB-2.5D. 18F-FP-2.5D and 18F-FP-2.5F enabled integrin-specific PET imaging of U87MG tumors with good imaging contrasts. 18F-FP-2.5D demonstrated more desirable pharmacokinetics compared to 18F-FP-2.5F, and thus has greater potential for clinical translation.
登录
查看更多内容
影响因子：
2.9
作者：
Kimura RH;Levin AM;Cochran FV;Cochran JR
通讯作者：
Cochran JR
影响因子：
9.3
作者：
Kenny, Laura M.;Coombes, R. Charles;Aboagye, Eric O.
通讯作者：
Aboagye, Eric O.
影响因子：
37.8
作者：
Ellegala, DB;Poi, HL;Lindner, JR
通讯作者：
Lindner, JR
影响因子：
11.2
作者：
Chen, XY;Conti, PS;Moats, RA
通讯作者：
Moats, RA
影响因子：
12.4
作者：
Beer AJ;Kessler H;Wester HJ;Schwaiger M
通讯作者：
Schwaiger M