111In-labeled cystine-knot peptides based on the Agouti-related protein for targeting tumor angiogenesis.
111In-labeled cystine-knot peptides based on the Agouti-related protein for targeting tumor angiogenesis.
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111In 标记的胱氨酸结肽基于 Agouti 相关蛋白，用于靶向肿瘤血管生成。
DOI：
10.1155/2012/368075
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发表时间：
2012
影响因子：
--
通讯作者：
Cheng Z
中科院分区：
文献类型：
--
作者：
Jiang L;Miao Z;Kimura RH;Silverman AP;Ren G;Liu H;Lu H;Cochran JR;Cheng Z
Agouti-related protein（AgRP）是一种人源的4-kDa胱氨酸结肽，具有4个二硫键和4个溶剂暴露环。细胞粘附受体整合素αvβ3是一种重要的肿瘤血管生成因子，决定了许多恶性肿瘤的侵袭和转移能力。AgRP突变体已经被工程化以使用定向进化以高亲和力和特异性结合整联蛋白αvβ3。在此，用111 In放射性标记AgRP突变体7 C和6 E，并评价其对肿瘤整合素αvβ3受体的体内靶向作用。将AgRP肽与金属螯合剂1，4，7，10-四氮杂环十二烷- N，N′，N″，N ′-四乙酸（DOTA）偶联，并用111 In标记。放射性肽111 In-DOTA-AgRP-7 C和111 In-DOTA-AgRP-6 E分别在磷酸盐缓冲盐水（PBS）和小鼠血清中测试稳定性。在U87 MG细胞系中进行放射性标记肽的细胞摄取测定。进行生物分布研究以使用携带表达整合素的U87 MG异种移植肿瘤的小鼠评价两种所得探针的体内性能。这两种AgRP肽易于用111 In标记，产率高，放射化学纯度>99%。这两种探针在磷酸盐缓冲液和小鼠血清中均表现出较高的稳定性。与111 In-DOTA-AgRP-6 E相比，111 In-DOTA-AgRP-7 C显示增加的U87 MG肿瘤摄取和更长的肿瘤保留（在0.5和24小时分别为5.74 ± 1.60和1.29 ± 0.02%ID/g），这与细胞摄取的测量结果一致。此外，111 In-DOTA-AgRP-7 C的肿瘤摄取通过与过量的整合素结合肽模拟物c（RGDyK）共注射而被特异性抑制。因此，111 In-DOTA-AgRP-7 C是靶向活体受试者中整合素αvβ3阳性肿瘤的有希望的探针。
Agouti-related protein (AgRP) is a 4-kDa cystine-knot peptide of human origin with four disulfide bonds and four solvent-exposed loops. The cell adhesion receptor integrin αvβ3 is an important tumor angiogenesis factor that determines the invasiveness and metastatic ability of many malignant tumors. AgRP mutants have been engineered to bind to integrin αvβ3 with high affinity and specificity using directed evolution. Here, AgRP mutants 7C and 6E were radiolabeled with 111In and evaluated for in vivo targeting of tumor integrin αvβ3 receptors. AgRP peptides were conjugated to the metal chelator 1, 4, 7, 10-tetra-azacyclododecane- N, N′, N″, N‴-tetraacetic acid (DOTA) and radiolabeled with 111In. The stability of the radiopeptides 111In-DOTA-AgRP-7C and 111In-DOTA-AgRP-6E was tested in phosphate-buffered saline (PBS) and mouse serum, respectively. Cell uptake assays of the radiolabeled peptides were performed in U87MG cell lines. Biodistribution studies were performed to evaluate the in vivo performance of the two resulting probes using mice bearing integrin-expressing U87MG xenograft tumors. Both AgRP peptides were easily labeled with 111In in high yield and radiochemical purity (>99%). The two probes exhibited high stability in phosphate-buffered saline and mouse serum. Compared with 111In-DOTA-AgRP-6E, 111In-DOTA-AgRP-7C showed increased U87MG tumor uptake and longer tumor retention (5.74 ± 1.60 and 1.29 ± 0.02%ID/g at 0.5 and 24 h, resp.), which was consistent with measurements of cell uptake. Moreover, the tumor uptake of 111In-DOTA-AgRP-7C was specifically inhibited by coinjection with an excess of the integrin-binding peptidomimetic c(RGDyK). Thus, 111In-DOTA-AgRP-7C is a promising probe for targeting integrin αvβ3 positive tumors in living subjects.
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影响因子：
--
作者：
Jackson, Pilgrim J.;Douglas, Nick R.;Millhauser, Glenn L.
通讯作者：
Millhauser, Glenn L.
影响因子：
9.3
作者：
Kumar, Senthil R.;Deutscher, Susan L.
通讯作者：
Deutscher, Susan L.
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
11.2
作者：
Cheng, Z;Chen, JQ;Jurisson, SS
通讯作者：
Jurisson, SS
DOI：
10.1007/s00259-010-1672-1
发表时间：
2011-04-01
影响因子：
9.1
作者：
Chang, Edwin;Liu, Shuangdong;Cheng, Zhen
通讯作者：
Cheng, Zhen