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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 [18 F]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 [18 F]Al-F gave 18 F-NP-F3. 18 F-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. 18 F-NP-F3 is reported as the first 18 F-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.

Original publication

DOI

10.1002/jlcr.3439

Type

Journal article

Journal

J Labelled Comp Radiopharm

Publication Date

10/2016

Volume

59

Pages

492 - 499

Keywords

F3, [18F]Al-F, endothelial cells, nucleolin receptor, transglutaminase, Amino Acid Sequence, Binding, Competitive, Biological Transport, Cell Line, Tumor, Chemistry Techniques, Synthetic, Drug Stability, Endothelial Cells, Fluorine Radioisotopes, Gene Expression Regulation, Neoplastic, Humans, Hydrophobic and Hydrophilic Interactions, Indium Radioisotopes, Isotope Labeling, Peptides, Phosphoproteins, RNA-Binding Proteins, Tissue Distribution