Synthesis and characterization of a melanoma-targeted fluorescence imaging probe by conjugation of a melanocortin 1 receptor (MC1R) specific ligand.
Synthesis and characterization of a melanoma-targeted fluorescence imaging probe by conjugation of a melanocortin 1 receptor (MC1R) specific ligand.
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DOI：
10.1021/bc300549s
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发表时间：
2012-12-19
影响因子：
4.7
通讯作者：
Vagner, Josef
中科院分区：
文献类型：
--
作者：
Tafreshi, Narges K.;Huang, Xuan;Moberg, Valerie E.;Barkey, Natalie M.;Sondak, Vernon K.;Tian, Haibin;Morse, David L.;Vagner, Josef
The incidence of malignant melanoma is rising faster than that of any other cancer in the United States. The melanocortin 1 receptor (MC1R) is overexpressed in most human melanoma metastases, thus making it a promising target for imaging and therapy of melanomas. We have previously reported the development of a peptidomimetic ligand with high specificity and affinity for MC1R. Here, we have conjugated near-infrared fluorescent dyes to the C-terminus of this ligand via lysine-mercaptopropionic acid linkers to generate MC1R specific optical probes (MC1RL-800, 0.4 nM Ki and MC1RL-Cy5, 0.3 nM Ki). Internalization of the imaging probe was studied in vitro by fluorescence microscopy using engineered A375/MC1R cells and B16F10 cells with endogenous MC1R expression. The in vivo tumor targeting of MC1RL-800 was evaluated by intravenous injection of probe into nude mice bearing bilateral subcutaneous A375 xenograft tumors with low MC1R expression and engineered A375/MC1R tumors with high receptor expression. Melanotic B16F10 xenofgrafts were also studied. Fluorescence imaging showed that the agent has higher uptake values in tumors with high expression compared to low (p<0.05), demonstrating the effect of expression levels on image contrast-to-noise. In addition, tumor uptake was significantly blocked by co-injection of excess NDP-α-MSH peptide (p<0.05). In conclusion, the MC1R-specific imaging probe developed in this study displays excellent potential for the intraoperative detection of regional node involvement and for margin detection during melanoma metastasis resection.
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影响因子：
3.1
作者：
Keereweer, Stijn;Kerrebijn, Jeroen D. F.;van Driel, Pieter B. A. A.;Xie, Bangwen;Kaijzel, Eric L.;Snoeks, Thomas J. A.;Que, Ivo;Hutteman, Merlijn;van der Vorst, Joost R.;Mieog, J. Sven D.;Vahrmeijer, Alexander L.;van de Velde, Cornelis J. H.;de Jong, Robert J. Baatenburg;Lowik, Clemens W. G. M.
通讯作者：
Lowik, Clemens W. G. M.
影响因子：
9
作者：
Kalady, MF;White, RR;Seigler, HF
通讯作者：
Seigler, HF
影响因子：
7.3
作者：
Cai, MY;Mayorov, AV;Hruby, VJ
通讯作者：
Hruby, VJ
影响因子：
2.7
作者：
Koikov, LN;Ebetino, FH;Knittel, JJ
通讯作者：
Knittel, JJ
影响因子：
2.9
作者：
Handl, HL;Vagner, J;Gillies, RJ
通讯作者：
Gillies, RJ