Synthesis and Evaluation of New Bifunctional Chelators with Phosphonic Acid Arms for Gallium-68 Based PET Imaging in Melanoma.
Synthesis and Evaluation of New Bifunctional Chelators with Phosphonic Acid Arms for Gallium-68 Based PET Imaging in Melanoma.
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DOI：
10.1021/acs.bioconjchem.8b00642
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发表时间：
2018-10-17
影响因子：
4.7
通讯作者：
Ma X
中科院分区：
文献类型：
--
作者：
Gai Y;Sun L;Lan X;Zeng D;Xiang G;Ma X
由于在正电子发射断层扫描/计算机断层扫描（PET/CT）中越来越多地使用发生器产生的放射性金属镓-68（68 Ga），因此非常需要能够有效地将68 Ga 3+掺入生物分子中的可靠的双功能螯合剂。在这项研究中，我们合成了两个新的双功能螯合剂带有一个或两个膦酸官能团，命名为p-SCN-PhPr-NE 2A 1 P和p-SCN-PhPr-NE 2 P1 A，目的是使68 Ga为基础的放射性药物的容易生产。两种螯合剂均成功地与LLP 2A-PEG 4（一种非常晚期抗原-4（VLA-4）靶向肽模拟配体）缀合，以评估它们在基于68 Ga的PET成像中的应用。NE 2 P1 A-PEG 4-LLP 2A在中性pH和温和温度下具有最高的68 Ga 3+结合能力，摩尔比为37 MBq/nmol，具有良好的血清稳定性，与密度泛函理论计算结果一致。体外细胞研究显示，与报道的64 Cu-NE 3 TA-PEG 4-LLP 2A的保留相比，68 Ga-NE 2 P1 A-PEG 4-LLP 2A在B16 F10细胞中具有显著更长的保留，尽管摄取相对较低。在生物分布和微PET/CT成像研究中，在将68 Ga-NE 2 P1 A-PEG 4-LLP 2A注射到携带B16 F10肿瘤异种移植物的小鼠中后观察到高肿瘤摄取和低背景，使其成为用于黑素瘤中过表达的VLA-4受体的非侵入性成像的非常有前途的放射性示踪剂。
Due to the increasing use of generator-produced radiometal Gallium-68 (68Ga) in positron-emission tomography/computed tomography (PET/CT), reliable bifunctional chelators that can efficiently incorporate 68Ga3+ into biomolecules are highly desirable. In this study, we synthesized two new bifunctional chelators bearing one or two phosphonic acid functional groups, named p-SCN-PhPr-NE2A1P and p-SCN-PhPr-NE2P1A, with the aim of enabling facile production of 68Ga-based radiopharmaceuticals. Both chelators were successfully conjugated to LLP2A-PEG4, a very late antigen-4 (VLA-4) targeting peptidomimetic ligand, to evaluate their application in 68Ga-based PET imaging. NE2P1A-PEG4-LLP2A exhibited the highest 68Ga3+ binding ability with molar activity of 37 MBq/nmol under mild temperature and neutral pH. Excellent serum stability of 68Ga-NE2P1A-PEG4-LLP2A was observed, which was consistent with the result obtained from density functional theory calculation. The in vitro cell study showed that 68Ga-NE2P1A-PEG4-LLP2Ahad significantly longer retention in B16F10 cells comparing to the reported retention of 64Cu-NE3TA-PEG4-LLP2A, although the uptake was relatively lower. In the biodistribution and micro-PET/CT imaging studies, high tumor uptake and low background were observed after 68Ga-NE2P1A-PEG4-LLP2A was injected into mice bearing B16F10 tumor xenografts, making it a highly promising radiotracer for noninvasive imaging of VLA-4 receptors overexpressed in melanoma.
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DOI：
10.3390/molecules201019393
发表时间：
2015-10-23
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Gai Y;Hu Z;Rong Z;Ma X;Xiang G
通讯作者：
Xiang G
影响因子：
4.3
作者：
Notni, Johannes;Hermann, Petr;Lukes, Ivan
通讯作者：
Lukes, Ivan
影响因子：
4.7
作者：
Chong, Hyun-Soon;Song, Hyun A.;Brechbiel, Martin W.
通讯作者：
Brechbiel, Martin W.
[68Ga]Ga-PSMA-HBED-CC 的新临床前和放射性药物方面：一种用于前列腺癌成像的新 PET 示踪剂。
DOI：
10.3390/ph7070779
发表时间：
2014-06-30
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Eder M;Neels O;Müller M;Bauder-Wüst U;Remde Y;Schäfer M;Hennrich U;Eisenhut M;Afshar-Oromieh A;Haberkorn U;Kopka K
通讯作者：
Kopka K
DOI：
10.2967/jnumed.114.144881
发表时间：
2014-11
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Beaino W;Anderson CJ
通讯作者：
Anderson CJ