Synthesis and characterization of a melanoma-targeted fluorescence imaging probe by conjugation of a melanocortin 1 receptor (MC1R) specific ligand.
Tafreshi. Narges K NK; Huang. Xuan X; Moberg. Valerie E VE; Barkey. Natalie M NM; Sondak. Vernon K VK; Tian. Haibin H; Morse. David L DL; Vagner. Josef J
Key Findings
- The team created fluorescent probes (MC1RL-800 and MC1RLâCy5) that bind MC1R with very high affinity (â0.3â0.4âŻnM).
- In mouse models, the probes accumulated more in tumors with high MC1R levels, giving clearer images.
- Coâinjecting excess MC1Râtargeting peptide blocked probe uptake, confirming the binding is specific.
Practical Outcomes
- The work shows a promising way to improve melanoma imaging during surgery, but it offers no actionable protocol, dosage, or health benefit for selfâexperimenters or the general public.
Summary
Scientists made a glowing molecule that sticks to a protein often found on melanoma skin cancers, letting surgeons see tumors more clearly during operations. This is a research tool, not a supplement or treatment you can use yourself.
Abstract
The incidence of malignant melanoma is rising more rapidly 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 K(i); and MC1RL-Cy5, 0.3 nM K(i)). 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 xenografts 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 coinjection 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.
Study Information
pubmed
2012
2012-11-27T00:00:00.000Z
10.1021/bc300549s
32
51