Radiobrominated benzimidazole-quinoline derivatives as Platelet-derived growth factor receptor beta (PDGFRβ) imaging probes.
Radiobrominated benzimidazole-quinoline derivatives as Platelet-derived growth factor receptor beta (PDGFRβ) imaging probes.
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DOI：
10.1038/s41598-018-28529-0
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发表时间：
2018-07-10
影响因子：
4.6
通讯作者：
Ogawa K
中科院分区：
文献类型：
--
作者：
Effendi N;Mishiro K;Takarada T;Makino A;Yamada D;Kitamura Y;Shiba K;Kiyono Y;Odani A;Ogawa K
血小板源性生长因子受体β（PDGFRβ）影响许多人类癌症，并且已被认为是癌症治疗的有希望的分子靶点。PDGFRβ的过度表达可作为肿瘤诊断的生物标志物。对分子靶点具有高亲和力的放射性标记配体可能是用于肿瘤中过表达受体成像的有用工具。在这项研究中，我们的目的是开发放射性溴化PDGFRβ配体，并评估其作为PDGFRβ成像探针的有效性。放射性标记的配体是通过修饰1-{2-[5-（2-甲氧基乙氧基）-1H-苯并[d]咪唑-1-基]喹啉-8-基}哌啶-4-胺（1）设计的，其显示出对PDGFRβ的选择性抑制特征。溴原子直接引入到1的喹啉基团的C-5中，或通过1与3-溴苯甲酰基的共轭间接引入。[77 Br]1-{5-溴-2-[5-（2-甲氧基乙氧基）-1H-苯并[d]咪唑-1-基]喹啉-8-基}哌啶-4-胺（[77 Br]2）和[77 Br]-N-3-溴苯甲酰基-1-{2-[5-（2-甲氧基乙氧基）-1H-苯并[d]咪唑-1-基]喹啉-8-基}-哌啶-4-胺（[77 Br]3）使用溴代去锡烷基化反应制备。在一项细胞摄取研究中，[77 Br]2和[77 Br]3在BxPC 3-luc细胞（PDGFRβ阳性）中的蓄积量高于MCF 7细胞（PDGFR β阴性），且抑制剂预处理可显著降低其蓄积量。在生物分布实验中，注射后1 h，[77 Br]2的积累高于[77 Br]3的积累。这些发现表明，[76 Br]2比[76 Br]3更有希望用于PDGFRβ的正电子发射断层扫描（PET）成像。
Platelet-derived growth factor receptor beta (PDGFRβ) affects in numerous human cancers and has been recognized as a promising molecular target for cancer therapies. The overexpression of PDGFRβ could be a biomarker for cancer diagnosis. Radiolabeled ligands having high affinity for the molecular target could be useful tools for the imaging of overexpressed receptors in tumors. In this study, we aimed to develop radiobrominated PDGFRβ ligands and evaluate their effectiveness as PDGFRβ imaging probes. The radiolabeled ligands were designed by modification of 1-{2-[5-(2-methoxyethoxy)-1H- benzo[d]imidazol-1-yl]quinolin-8-yl}piperidin-4-amine (1), which shows selective inhibition profile toward PDGFRβ. The bromine atom was introduced directly into C-5 of the quinoline group of 1, or indirectly by the conjugation of 1 with the 3-bromo benzoyl group. [77Br]1-{5-Bromo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinoline-8-yl}piperidin-4-amine ([77Br]2) and [77Br]-N-3-bromobenzoyl-1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}-piperidin-4-amine ([77Br]3) were prepared using a bromodestannylation reaction. In a cellular uptake study, [77Br]2 and [77Br]3 more highly accumulatd in BxPC3-luc cells (PDGFRβ-positive) than in MCF7 cells (PDGFRβ-negative), and their accumulation was significantly reduced by pretreatment with inhibitors. In biodistribution experiments, [77Br]2 accumulation was higher than [77Br]3 accumulation at 1 h postinjection. These findings suggest that [76Br]2 is more promising for positron emission tomography (PET) imaging of PDGFRβ than [76Br]3.
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影响因子：
3.2
作者：
Ogawa K;Kanbara H;Shiba K;Kitamura Y;Kozaka T;Kiwada T;Odani A
通讯作者：
Odani A
影响因子：
3.7
作者：
Ogawa K;Ishizaki A;Takai K;Kitamura Y;Kiwada T;Shiba K;Odani A
通讯作者：
Odani A
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
3.1
作者：
Kil, Kun-Eek;Ding, Yu-Shin;Fowler, Joanna S.
通讯作者：
Fowler, Joanna S.
影响因子：
50.3
作者：
Pietras, K;Sjöblom, T;Östman, A
通讯作者：
Östman, A