Synthesis and evaluation of an 18F-labeled derivative of F3 for targeting surface-expressed nucleolin in cancer and tumor endothelial cells

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Abstract

The surface overexpression of nucleolin provides an anchor for the specific attachment of biomolecules to cancer and angiogenic endothelial cells. The peptide F3 is a high-affinity ligand of the nucleolin receptor (NR) that has been investigated as a carrier to deliver biologically active molecules to tumors for both therapeutic and imaging applications. A site-specific PEGylated F3 derivative was radiolabeled with [18F]Al-F. The binding affinity and cellular distribution of the compound was assessed in tumor (H2N) and tumor endothelial (2H-11) cells. Specific uptake via the NR was demonstrated by the siRNA knockdown of nucleolin in both cell lines. The partition and the plasma stability of the compound were assessed at 37°C. The enzyme-mediated site-specific modification of F3 to give NODA-PEG-F3 (NP-F3) was achieved. Radiolabeling with [18F]Al-F gave 18F-NP-F3. 18F-NP-F3 demonstrated high affinity for cancer and tumor endothelial cells. The siRNA knockdown of nucleolin resulted in a binding affinity reduction of 50% to 60%, confirming cell surface binding via the NR. NP-F3 was stable in serum for 2 h. 18F-NP-F3 is reported as the first 18F-labeled F3 derivative. It was obtained in a site-specific, high-yield, and efficient manner and binds to surface NR in the low nanomolar range, suggesting it has potential as a tumor and angiogenesis tracer.

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Lam, P. Y. H., Hillyar, C. R. T., Able, S., & Vallis, K. A. (2016). Synthesis and evaluation of an 18F-labeled derivative of F3 for targeting surface-expressed nucleolin in cancer and tumor endothelial cells. Journal of Labelled Compounds and Radiopharmaceuticals, 492–499. https://doi.org/10.1002/jlcr.3439

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