Melanoma-Targeting Property of Y-90-Labeled Lactam-Cyclized α-Melanocyte-Stimulating Hormone Peptide
Melanoma-Targeting Property of Y-90-Labeled Lactam-Cyclized α-Melanocyte-Stimulating Hormone Peptide
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DOI：
10.1089/cbr.2019.3049
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发表时间：
2019-11-01
影响因子：
3.4
通讯作者：
Miao, Yubin
中科院分区：
文献类型：
--
作者：
Xu, Jingli;Yang, Jianquan;Miao, Yubin
目的：本研究的目的是评估Y-90-DOTA-GGNle-CycMSH（hex）的黑色素瘤靶向性，以促进其潜在的治疗应用。材料与方法：合成DOTA-GGNle-CycMSH（hex），并在0.25 M NH 4Ac缓冲溶液中容易地用Y-90标记以产生Y-90-DOTA-GGNle-CycMSH（hex）。在B16/F10鼠黑素瘤细胞上测定Y-90-DOTA-GGNle-CycMSH（hex）的特异性受体结合、内化和流出。在携带B16/F10黑素瘤的C57小鼠上检查Y-90-DOTA-GGNle-CycMSH（hex）的生物分布特性。结果：Y-90-DOTA-GGNle-CycMSH（hex）在B16/F10黑色素瘤细胞上显示受体特异性结合、快速内化和延长的外排。Y-90-DOTA-GGNle-CycMSH（hex）在黑色素瘤中表现出高吸收和延长保留，并且在携带B16/F10黑色素瘤的C57小鼠中表现出快速尿液清除。注射后0.5、2、4和24 h，B16/F10肿瘤摄取分别为20.73% +/-7.99%、19.93% +/-5.73%、14.8% +/-4.61%和6.69% +/- 1.85% ID/g。结论：Y-90-DOTA-GGNle-CycMSH（hex）对B16/F10黑色素瘤细胞和肿瘤具有黑皮质素受体（MC 1 R）靶向性和特异性。Y-90-DOTA-GGNle-CycMSH（hex）有利的黑素瘤靶向性质和快速的尿清除保证了其在未来研究中用于黑素瘤治疗的评价。
Purpose: The purpose of this study was to evaluate melanoma-targeting property of Y-90-DOTA-GGNle-CycMSH(hex) to facilitate its potential therapeutic application. Materials and Methods: DOTA-GGNle-CycMSH(hex) was synthesized and readily labeled with Y-90 in 0.25 M NH4Ac-buffered solution to generate Y-90-DOTA-GGNle-CycMSH(hex). The specific receptor binding, internalization, and efflux of Y-90-DOTA-GGNle-CycMSH(hex) were determined on B16/F10 murine melanoma cells. The biodistribution property of Y-90-DOTA-GGNle-CycMSH(hex) was examined on B16/F10 melanoma-bearing C57 mice. Results: Y-90-DOTA-GGNle-CycMSH(hex) displayed receptor-specific binding, rapid internalization, and prolonged efflux on B16/F10 melanoma cells. Y-90-DOTA-GGNle-CycMSH(hex) exhibited high uptake and prolonged retention in melanoma, and fast urinary clearance on B16/F10 melanoma-bearing C57 mice. The B16/F10 tumor uptake was 20.73% +/- 7.99%, 19.93% +/- 5.73%, 14.8% +/- 4.61%, and 6.69% +/- 1.85% ID/g at 0.5, 2, 4, and 24 h postinjection, respectively. Conclusions: Y-90-DOTA-GGNle-CycMSH(hex) displayed melanocortin-1 receptor (MC1R) targeting and specificity on B16/F10 melanoma cells and tumors. The favorable melanoma-targeting property and fast urinary clearance of Y-90-DOTA-GGNle-CycMSH(hex) warranted its evaluation for melanoma therapy in future studies.