Multi-modal imaging for uptake of peptide ligand specific for CD44 by hepatocellular carcinoma

肝细胞癌对 CD44 特异性肽配体的摄取的多模态成像

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作者:Xiaoli Wu, Xiaoqing Meng, Tse-Shao Chang, Shuo Feng, Miki Lee, Sangeeta Jaiswal, Eun-Young K Choi, Lam Tran, Hui Jiang, Thomas D Wang

Background

Hepatocellular carcinoma (HCC) is rising steadily in incidence, and more effective

Conclusions

We have identified a peptide specific for CD44 with properties that are promising for clinical translation to image HCC in vivo.

Methods

We used a structural model to optimize the peptide sequence. Specific binding was validated in vitro with knockdown, competition, and co-localization assays. Multi-modal imaging was performed to validate specific binding in vivo in orthotopically-implanted human xenograft tumors.

Results

Binding properties of WKGWSYLWTQQA were characterized by an apparent dissociation constant of kd = 43 nM, and an apparent association time constant of k = 0.26 min-1. The target-to-background ratio was significantly higher for the target versus control for both modalities. Ex-vivo evaluation using human HCC specimens supported the ability of the peptide to distinguish HCC from other liver pathologies. Conclusions: We have identified a peptide specific for CD44 with properties that are promising for clinical translation to image HCC in vivo.

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