一种靶向胃泌素释放肽受体的高亲和力近红外荧光探针。
A high-affinity near-infrared fluorescent probe to target bombesin receptors.
作者信息
Shrivastava Ajay, Ding Haiming, Kothandaraman Shankaran, Wang Shu-Huei, Gong Li, Williams Michelle, Milum Keisha, Zhang Song, Tweedle Michael F
机构信息
Department of Radiology, The Ohio State University, Columbus, OH, 43210, USA.
出版信息
Mol Imaging Biol. 2014 Oct;16(5):661-9. doi: 10.1007/s11307-014-0727-2.
PURPOSE
This study aimed to create new optical surgical navigation NIRF probes for prostate and breast cancers.
PROCEDURES
IR800-linker-QWAVGHLM-NH2 with linker = GSG, GGG, and G-Abz4 were synthesized and characterized. IC50 for bombesin receptors (BBN-R) in PC-3 prostate and T47D breast cancer cells, fluorescence microscopy in PC-3 cells, and NIRF imaging in mice PC-3 tumor xenografts were studied.
RESULTS
GGG, GSG, and G-Abz4 derivatives had IC50 (nM) for BBN-R+ PC-3 cells = 187 ± 31, 56 ± 5, and 2.6 ± 0.2 and T47D cells = 383 ± 1, 57.4 ± 1.2, and 3.1 ± 1.1, respectively. By microscopy the Abz4 derivative showed the highest uptake, was competed with by BBN, and had little to no binding to BBN-R- cells. In NIRF imaging the G-Abz4 probe was brighter than GGG probe in BBN-R+ tissues in vivo and tissues, tumors, and tumor slices ex vivo. Uptake could be partially blocked in BBN-R+ pancreas but not visibly in tumor.
CONCLUSIONS
Linker choice can dominate peptidic BBN-R binding. The G-Abz4 linker yields a higher affinity and specific BBN-R binder in this series of molecules.
目的
本研究旨在开发用于前列腺癌和乳腺癌的新型光学手术导航近红外荧光（NIRF）探针。
程序
合成并表征了连接子分别为GSG、GGG和G-Abz4的IR800-连接子-QWAVGHLM-NH2。研究了其对PC-3前列腺癌细胞和T47D乳腺癌细胞中胃泌素释放肽受体（BBN-R）的半数抑制浓度（IC50）、PC-3细胞中的荧光显微镜观察以及小鼠PC-3肿瘤异种移植模型中的近红外荧光成像。
结果
GGG、GSG和G-Abz4衍生物对BBN-R阳性PC-3细胞的IC50（nM）分别为187±31、56±5和2.6±0.2，对T47D细胞的IC50分别为383±1、57.4±1.2和3.1±1.1。通过显微镜观察，Abz4衍生物的摄取量最高，可被BBN竞争，且与BBN-R阴性细胞几乎没有结合。在近红外荧光成像中，G-Abz4探针在体内BBN-R阳性组织以及离体的组织、肿瘤和肿瘤切片中比GGG探针更亮。在BBN-R阳性胰腺中摄取可被部分阻断，但在肿瘤中无明显可见的阻断。
结论
连接子的选择可主导肽类与BBN-R的结合。在这一系列分子中，G-Abz4连接子产生了具有更高亲和力和特异性的BBN-R结合剂。
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