Imaging integrin alpha-v-beta-3 expression in tumors with an 18F-labeled dimeric RGD peptide.
Imaging integrin alpha-v-beta-3 expression in tumors with an 18F-labeled dimeric RGD peptide.
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DOI：
10.1002/cmmi.1523
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发表时间：
2013-05
影响因子：
--
通讯作者：
Boerman, Otto C.
中科院分区：
文献类型：
--
作者：
Dijkgraaf, Ingrid;Terry, Samantha Y. A.;McBride, William J.;Goldenberg, David M.;Laverman, Peter;Franssen, Gerben M.;Oyen, Wim J. G.;Boerman, Otto C.
整合素αvβ3受体在新生血管形成期间在活化的内皮细胞上表达以维持肿瘤生长。许多放射性标记的探针利用精氨酸-甘氨酸-酒石酸（RGD）肽和整联蛋白αvβ3之间的紧密和特异性结合，但这些探针的任何临床应用的一个主要障碍是18 F的费力的多步放射合成。在这项研究中，二聚体的RGD肽，E-[c（RGDfK）]2，与NODAGA结合，并在一个简单的一锅法与放射性标记产率为20%的18 F标记，整个过程仅持续45分钟。NODAGA-E-[c（RGDfK）]2标记的18 F，比活度为1.8 MBq/nmol，放射化学纯度为100%，可以实现。18F标记的NODAGA-E-[c（RGDfK）]2的Log P值为−4.26 ± 0.02。在生物分布研究中，18 F-NODAGA-E-[c（RGDfK）]2在注射后2小时从血液中快速清除，血液中的ID/g为0.03 ± 0.01%，主要通过肾脏，并显示出良好的体内稳定性。18F-NODAGA-E-[c（RGDfK）]2的肿瘤摄取（3.44 ± 0.20% ID/g，2 h p.i.）68 Ga标记的NODAGA-E-[c（RGDfK）]2（6.26 ± 0.76% ID/g; P <0.001）和111 In标记的NODAGA-E-[c（RGDfK）]2（4.99 ± 0.64% ID/g; P < 0.01）显著低于对照化合物。将过量未标记NODAGA-E-[c（RGDfK）]2沿着与18 F-NODAGA-E-[c（RGDfK）]2共注射导致肿瘤中放射性浓度显著降低（0.85 ± 0.13% ID/g）。表达αvβ3整合素的SK-RC-52肿瘤可通过18 F标记的NODAGA-E-[c（RGDfK）]2的microPET成功可视化。总之，NODAGA-E-[c（RGDfK）]2可使用直接水性一锅法快速标记18 F，并在表达αvβ3整联蛋白的SK-RC-52肿瘤中特异性蓄积，允许通过microPET可视化。
Integrin αvβ3 receptors are expressed on activated endothelial cells during neovascularization to maintain tumor growth. Many radiolabeled probes utilize the tight and specific association between the arginine-glycine-aspartatic acid (RGD) peptide and integrin αvβ3, but one main obstacle for any clinical application of these probes is the laborious multistep radiosynthesis of 18F. In this study, the dimeric RGD peptide, E-[c(RGDfK)]2, was conjugated with NODAGA and radiolabeled with 18F in a simple one-pot process with a radiolabeling yield of 20%; the whole process lasting only 45 min. NODAGA-E-[c(RGDfK)]2 labeled with 18F at a specific activity of 1.8 MBq/nmol and a radiochemical purity of 100% could be achieved. Log P value of 18F-labeled NODAGA-E-[c(RGDfK)]2 was −4.26 ± 0.02. In biodistribution studies, 18F-NODAGA-E-[c(RGDfK)]2 cleared rapidly from the blood with 0.03 ± 0.01 %ID/g in the blood at 2 h p.i., mainly via the kidneys and showed good in vivo stability. Tumor uptake of 18F-NODAGA-E-[c(RGDfK)]2 (3.44 ± 0.20 %ID/g, 2 h p.i.) was significantly lower than that of reference compounds 68Ga-labeled NODAGA-E-[c(RGDfK)]2 (6.26 ± 0.76 %ID/g; P <0.001) and 111In-labeled NODAGA-E-[c(RGDfK)]2 (4.99 ± 0.64 %ID/g; P < 0.01). Co-injection of an excess of unlabeled NODAGA-E-[c(RGDfK)]2 along with 18F-NODAGA-E-[c(RGDfK)]2 resulted in significantly reduced radioactivity concentrations in the tumor (0.85 ± 0.13 %ID/g). The αvβ3 integrin-expressing SK-RC-52 tumor could be successfully visualized by microPET with 18F-labeled NODAGA-E-[c(RGDfK)]2. In conclusion, NODAGA-E-[c(RGDfK)]2 could be labeled rapidly with 18F using a direct aqueous, one-pot method and it accumulated specifically in αvβ3 integrin-expressing SK-RC-52 tumors, allowing for visualization by microPET.
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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：
4.7
作者：
Lang, Lixin;Li, Weihua;Guo, Ning;Ma, Ying;Zhu, Lei;Kiesewetter, Dale O.;Shen, Baozhong;Niu, Gang;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
使用一步标记的整合素靶向示踪剂 18F-AlF-NOTA-PRGD2 对心肌梗塞/再灌注后的血管生成进行 PET 成像。
DOI：
10.1007/s00259-011-2052-1
发表时间：
2012-04
影响因子：
9.1
作者：
Gao, Haokao;Lang, Lixin;Guo, Ning;Cao, Feng;Quan, Qimeng;Hu, Shuo;Kiesewetter, Dale O.;Niu, Gang;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
DOI：
10.2967/jnumed.109.066902
发表时间：
2010-03
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Laverman P;McBride WJ;Sharkey RM;Eek A;Joosten L;Oyen WJ;Goldenberg DM;Boerman OC
通讯作者：
Boerman OC
DOI：
10.1007/s00259-009-1122-0
发表时间：
2009-09-01
影响因子：
9.1
作者：
Hultsch, Christina;Schottelius, Margret;Wester, Hans-Juergen
通讯作者：
Wester, Hans-Juergen