(99m)Tc-Galacto-RGD2: a novel 99mTc-labeled cyclic RGD peptide dimer useful for tumor imaging.
(99m)Tc-Galacto-RGD2: a novel 99mTc-labeled cyclic RGD peptide dimer useful for tumor imaging.
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DOI：
10.1021/mp400085d
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发表时间：
2013-09-03
影响因子：
4.9
通讯作者：
Liu S
中科院分区：
文献类型：
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作者：
Ji S;Czerwinski A;Zhou Y;Shao G;Valenzuela F;Sowiński P;Chauhan S;Pennington M;Liu S
本研究旨在评价[99 mTc（HYNIC-半乳糖-RGD 2）（tricine）（TPPTS）]（99 mTc-半乳糖-RGD 2：HYNIC = 6-肼基烟碱基;半乳糖-RGD 2 = Glu[环[Arg-Gly-Asp-D-Phe-Lys（SAA-PEG 2-（1，2，3-三唑）-1-基-4-甲基酰胺）]2（SAA = 7-氨基-L-甘油基-L-半乳糖基-2，6-脱水-7-脱氧-庚酰胺，PEG 2 = 3，6-二氧杂辛酸）; TPPTS =三苯基膦-3，3 '，3”-三磺酸三钠）作为新的放射性示踪剂用于肿瘤成像。半乳糖-RGD 2是通过铜（I）催化的1，3-偶极叠氮-炔Huisgen环加成反应制备的。在二异丙基乙胺存在下，通过将半乳糖-RGD 2与琥珀酰亚胺基6-（2-（2-磺酸基苯甲醛）亚肼基）烟酸钠（HYNIC-OSu）反应制备HYNIC-半乳糖-RGD 2，并评价其整合素αvβ3对与U87 MG胶质瘤细胞结合的125 I-echistatin的结合亲和力。HYNIC-Galacto-RGD 2的IC 50值测定为20 ± 2 nM。制备了高比活度（~185 GBq/µmol）和高放射化学纯度（>95%）的99 mTc-Galacto-RGD 2，并在荷U87 MG胶质瘤异种移植物的无胸腺裸鼠中评价了其肿瘤靶向能力和生物分布。在注射后5、30、60和120 min，99 mTc-半乳糖-RGD 2的肿瘤摄取分别为10.30 ± 1.67、8.37 ± 2.13、6.86 ± 1.33和5.61 ± 1.52% ID/g，与整合素αvβ3在胶质瘤细胞和新生血管中的高表达相一致。其在肠、肺和脾中的较低摄取表明，99 mTc-半乳糖-RGD 2在胸部和腹部区域的肿瘤成像方面优于99 mTc-3 P-RGD 2（[99 mTc（HYNIC-3 P-RGD 2）（tricine）（TPPTS）]：3 P-RGD 2 = PEG 4-E[PEG 4-c（RGDfK）]2; PEG 4 = 15-氨基-4，7，10，13-四氧杂十五烷酸）。U87 MG肿瘤易于通过SPECT检测，并且99 mTc-Galacto-RGD 2的肿瘤摄取是整合素αvβ3特异性的。99 mTc-Galacto-RGD 2也具有非常高的代谢稳定性。根据本研究的结果，可以得出结论，99 mTc-Galacto-RGD 2是一种用于整合素αvβ3阳性肿瘤和相关转移瘤成像的极佳放射性示踪剂。
This study sought to evaluate [99mTc(HYNIC-Galacto-RGD2)(tricine)(TPPTS)] (99mTc-Galacto-RGD2: HYNIC = 6-hydrazinonicotinyl; Galacto-RGD2 = Glu[cyclo[Arg-Gly-Asp-D-Phe-Lys(SAA-PEG2-(1,2,3-triazole)-1-yl-4-methylamide)]]2 (SAA = 7-amino-L-glycero-L-galacto-2,6-anhydro-7-deoxy-heptanamide, and PEG2 = 3,6-dioxaoctanoic acid); and TPPTS = trisodium triphenylphosphine-3,3',3"-trisulfonate) as a new radiotracer for tumor imaging. Galacto-RGD2 was prepared via the copper (I)-catalyzed 1,3-dipolar azide–alkyne Huisgen cycloaddition. HYNIC-Galacto-RGD2 was prepared by reacting Galacto-RGD2 with sodium succinimidyl 6-(2-(2-sulfonatobenzaldehyde)hydrazono)nicotinate (HYNIC-OSu) in the presence of diisopropylethylamine, and was evaluated for its integrin αvβ3 binding affinity against 125I-echistatin bound to U87MG glioma cells. The IC50 value for HYNIC-Galacto-RGD2 was determined to be 20 ± 2 nM. 99mTc-Galacto-RGD2 was prepared in high specific activity (~185 GBq/µmol) and high radiochemical purity (>95%), and was evaluated in athymic nude mice bearing U87MG glioma xenografts for its tumor-targeting capability and biodistribution. The tumor uptake of 99mTc-Galacto-RGD2 was 10.30 ± 1.67, 8.37 ± 2.13, 6.86 ± 1.33 and 5.61 ± 1.52 %ID/g at 5, 30, 60 and 120 min p.i., respectively, which was in agreement with high integrin αvβ3 expression on glioma cells and neovasculature. Its lower uptake in intestines, lungs and spleen suggests that 99mTc-Galacto-RGD2 has advantages over 99mTc-3P–RGD2 ([99mTc(HYNIC-3P–RGD2)(tricine)(TPPTS)]: 3P–RGD2 = PEG4-E[PEG4-c(RGDfK)]2; PEG4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) for imaging tumors in the chest and abdominal regions. U87MG tumors were readily detected by SPECT and the tumor uptake of 99mTc-Galacto-RGD2 was integrin αvβ3-specific. 99mTc-Galacto-RGD2 also had very high metabolic stability. On the basis of results from this study, it was concluded that 99mTc-Galacto-RGD2 is an excellent radiotracer for imaging integrin αvβ3-positive tumors and related metastases.
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影响因子：
4.7
作者：
Chakraborty, Sudipta;Shi, Jiyun;Kim, Young-Seung;Zhou, Yang;Jia, Bing;Wang, Fan;Liu, Shuang
通讯作者：
Liu, Shuang
通过点击化学合成的1,2,3-三唑功能的核酸衍生物的化学结构和应用。
DOI：
10.3390/molecules171112665
发表时间：
2012-10-26
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Efthymiou T;Gong W;Desaulniers JP
通讯作者：
Desaulniers JP
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
4.7
作者：
Liu S
通讯作者：
Liu S
DOI：
10.2967/jnumed.111.088955
发表时间：
2012-05
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Doss M;Kolb HC;Zhang JJ;Bélanger MJ;Stubbs JB;Stabin MG;Hostetler ED;Alpaugh RK;von Mehren M;Walsh JC;Haka M;Mocharla VP;Yu JQ
通讯作者：
Yu JQ