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 [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.
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Authors | Phoebe Y H Lam, Christopher R T Hillyar, Sarah Able, Katherine A Vallis |
Journal | Journal of labelled compounds & radiopharmaceuticals
(J Labelled Comp Radiopharm)
Vol. 59
Issue 12
Pg. 492-499
(10 2016)
ISSN: 1099-1344 [Electronic] England |
PMID | 27594091
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2016 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons, Ltd. |
Chemical References |
- Fluorine Radioisotopes
- Indium Radioisotopes
- Peptides
- Phosphoproteins
- RNA-Binding Proteins
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Topics |
- Amino Acid Sequence
- Binding, Competitive
- Biological Transport
- Cell Line, Tumor
- Chemistry Techniques, Synthetic
- Drug Stability
- Endothelial Cells
(metabolism)
- Fluorine Radioisotopes
- Gene Expression Regulation, Neoplastic
- Humans
- Hydrophobic and Hydrophilic Interactions
- Indium Radioisotopes
- Isotope Labeling
- Peptides
(chemical synthesis, chemistry, metabolism, pharmacokinetics)
- Phosphoproteins
(metabolism)
- RNA-Binding Proteins
(metabolism)
- Tissue Distribution
- Nucleolin
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