当前位置：
X-MOL 学术
›
Mol. Pharmaceutics
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Novel [99mTc]-Tricarbonyl-NOTA-Conjugated Lactam-Cyclized Alpha-MSH Peptide with Enhanced Melanoma Uptake and Reduced Renal Uptake.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-07-14 , DOI: 10.1021/acs.molpharmaceut.0c00606 Zheng Qiao , Jingli Xu , Rene Gonzalez , Yubin Miao
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-07-14 , DOI: 10.1021/acs.molpharmaceut.0c00606 Zheng Qiao , Jingli Xu , Rene Gonzalez , Yubin Miao
|
The purpose of this study was to examine the melanoma targeting and imaging properties of 99mTc(CO)3-NOTA-GGNle-CycMSHhex {1,4,7-triazacyclononane-1,4,7-triyl-triacetic acid-GlyGlyNle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} and 99mTc(CO)3-NODAGA-GGNle-CycMSHhex {1,4,7-triazacyclononane,1-gluteric acid-4,7-acetic acid-GlyGlyNle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} on B16/F10 melanoma-bearing C57 mice to demonstrate the feasibility of NOTA/NODAGA as metal chelators for 99mTc(CO)3+ radiolabeling. NOTA/NODAGA-GGNle-CycMSHhex were synthesized using fluorenylmethoxycarbonyl (Fmoc) chemistry. The melanocortin-1 (MC1) receptor binding affinities of the peptides were determined on B16/F10 melanoma cells. The biodistribution of 99mTc(CO)3-NOTA-GGNle-CycMSHhex and 99mTc(CO)3-NODAGA-GGNle-CycMSHhex were determined on B16/F10 melanoma-bearing C57 mice at 2 h postinjection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of 99mTc(CO)3-NOTA-GGNle-CycMSHhex and 99mTc(CO)3-NODAGA-GGNle-CycMSHhex were determined on B16/F10 melanoma-bearing C57 mice. The IC50 values of NOTA/NODAGA-GGNle-CycMSHhex were 0.8 ± 0.1 and 0.9 ± 0.1 nM on B16/F10 cells. 99mTc(CO)3-NOTA-GGNle-CycMSHhex and 99mTc(CO)3-NODAGA-GGNle-CycMSHhex were readily prepared via the [99mTc(CO)3(OH2)3]+ intermediate and displayed MC1R-specific binding on B16/F10 cells. 99mTc(CO)3-NOTA-GGNle-CycMSHhex was further evaluated as a lead peptide because of its higher tumor uptake (19.76 ± 3.62% ID/g) and lower kidney uptake (1.59 ± 0.52% ID/g) at 2 h postinjection than 99mTc(CO)3-NODAGA-GGNle-CycMSHhex. The B16/F10 melanoma uptake of 99mTc(CO)3-NOTA-GGNle-CycMSHhex was 16.07 ± 4.47, 19.76 ± 3.62, 11.30 ± 2.81, and 3.16 ± 2.28% ID/g at 0.5, 2, 4, and 24 h postinjection, respectively. 99mTc(CO)3-NOTA-GGNle-CycMSHhex showed high tumor to normal organ uptake ratios after 2 h postinjection. The B16/F10 melanoma lesions were clearly visualized by SPECT/CT using 99mTc(CO)3-NOTA-GGNle-CycMSHhex as an imaging probe at 2 h postinjection. High tumor uptake, low kidney uptake, and fast urinary clearance of 99mTc(CO)3-NOTA-GGNle-CycMSHhex highlighted its potential for melanoma imaging and facilitated the evaluation of 188Re(CO)3-NOTA-GGNle-CycMSHhex for melanoma therapy.
中文翻译：
新型 [99mTc]-三羰基-NOTA 共轭内酰胺环化 α-MSH 肽，具有增强的黑色素瘤摄取和降低的肾摄取。
本研究的目的是检查99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex {1,4,7- triazacyclononane- 1,4,7- triyl-tri乙酸-GlyGlyNle-的黑色素瘤靶向和成像特性c[Asp-His-DPhe-Arg-Trp-Lys]-CONH 2 } 和99m Tc(CO) 3 -NODAGA-GGNle-CycMSH hex {1,4,7-triazacyclononane,1-gluteric acid-4,7-乙酸-GlyGlyNle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH 2 } 在携带 B16/F10 黑色素瘤的 C57 小鼠身上证明了 NOTA/NODAGA 作为99m Tc(CO) 3金属螯合剂的可行性+放射性标记。NOTA/NODAGA-GGNle-CycMSH hex使用芴基甲氧基羰基（Fmoc）化学合成。在 B16/F10 黑色素瘤细胞上测定了肽的黑皮质素-1 (MC1) 受体结合亲和力。99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex和99m Tc(CO) 3 -NODAGA-GGNle-CycMSH hex在 B16/F10 携带黑色素瘤的 C57 小鼠上的生物分布在注射后 2 小时确定以选择先导肽以供进一步评估。99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex和99m Tc(CO) 3 -NODAGA-GGNle-CycMSH hex的黑色素瘤靶向和成像特性对携带 B16/F10 黑色素瘤的 C57 小鼠进行测定。NOTA/NODAGA-GGNle-CycMSH hex的 IC 50值在 B16/F10 细胞上分别为 0.8 ± 0.1 和 0.9 ± 0.1 nM。99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex和99m Tc(CO) 3 -NODAGA-GGNle-CycMSH hex很容易通过 [ 99m Tc(CO) 3 (OH 2 ) 3 ] +中间体制备并展示 MC1R -对 B16/F10 细胞的特异性结合。99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex被进一步评估为先导肽，因为与99m Tc(CO) 3 -NODAGA-GGNle 相比，其在注射后 2 小时的肿瘤吸收率更高 (19.76 ± 3.62% ID/g) 和肾脏吸收率更低 (1.59 ± 0.52% ID/g) -CycMSH十六进制。B16/F10 黑色素瘤对99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex的吸收为 16.07 ± 4.47、19.76 ± 3.62、11.30 ± 2.81 和 3.16 ± 2.28% ID/g，4、4 和 2 h 注射后，分别。99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex在注射后 2 小时后显示出高肿瘤与正常器官摄取比率。B16/F10 黑色素瘤病变通过 SPECT/CT 使用99m Tc(CO) 3清晰可见-NOTA-GGNle-CycMSH hex作为注射后 2 小时的成像探针。99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex 的高肿瘤摄取、低肾脏摄取和快速尿清除突出了其黑色素瘤成像的潜力，并促进了188 Re(CO) 3 -NOTA-GGNle-CycMSH hex的评估用于黑色素瘤治疗。
更新日期：2020-09-09
中文翻译：
新型 [99mTc]-三羰基-NOTA 共轭内酰胺环化 α-MSH 肽，具有增强的黑色素瘤摄取和降低的肾摄取。
本研究的目的是检查99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex {1,4,7- triazacyclononane- 1,4,7- triyl-tri乙酸-GlyGlyNle-的黑色素瘤靶向和成像特性c[Asp-His-DPhe-Arg-Trp-Lys]-CONH 2 } 和99m Tc(CO) 3 -NODAGA-GGNle-CycMSH hex {1,4,7-triazacyclononane,1-gluteric acid-4,7-乙酸-GlyGlyNle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH 2 } 在携带 B16/F10 黑色素瘤的 C57 小鼠身上证明了 NOTA/NODAGA 作为99m Tc(CO) 3金属螯合剂的可行性+放射性标记。NOTA/NODAGA-GGNle-CycMSH hex使用芴基甲氧基羰基（Fmoc）化学合成。在 B16/F10 黑色素瘤细胞上测定了肽的黑皮质素-1 (MC1) 受体结合亲和力。99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex和99m Tc(CO) 3 -NODAGA-GGNle-CycMSH hex在 B16/F10 携带黑色素瘤的 C57 小鼠上的生物分布在注射后 2 小时确定以选择先导肽以供进一步评估。99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex和99m Tc(CO) 3 -NODAGA-GGNle-CycMSH hex的黑色素瘤靶向和成像特性对携带 B16/F10 黑色素瘤的 C57 小鼠进行测定。NOTA/NODAGA-GGNle-CycMSH hex的 IC 50值在 B16/F10 细胞上分别为 0.8 ± 0.1 和 0.9 ± 0.1 nM。99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex和99m Tc(CO) 3 -NODAGA-GGNle-CycMSH hex很容易通过 [ 99m Tc(CO) 3 (OH 2 ) 3 ] +中间体制备并展示 MC1R -对 B16/F10 细胞的特异性结合。99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex被进一步评估为先导肽，因为与99m Tc(CO) 3 -NODAGA-GGNle 相比，其在注射后 2 小时的肿瘤吸收率更高 (19.76 ± 3.62% ID/g) 和肾脏吸收率更低 (1.59 ± 0.52% ID/g) -CycMSH十六进制。B16/F10 黑色素瘤对99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex的吸收为 16.07 ± 4.47、19.76 ± 3.62、11.30 ± 2.81 和 3.16 ± 2.28% ID/g，4、4 和 2 h 注射后，分别。99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex在注射后 2 小时后显示出高肿瘤与正常器官摄取比率。B16/F10 黑色素瘤病变通过 SPECT/CT 使用99m Tc(CO) 3清晰可见-NOTA-GGNle-CycMSH hex作为注射后 2 小时的成像探针。99m Tc(CO) 3 -NOTA-GGNle-CycMSH hex 的高肿瘤摄取、低肾脏摄取和快速尿清除突出了其黑色素瘤成像的潜力，并促进了188 Re(CO) 3 -NOTA-GGNle-CycMSH hex的评估用于黑色素瘤治疗。
京公网安备 11010802027423号