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- Title
Synthesis and evaluation of an <sup>18</sup>F-labeled derivative of F3 for targeting surface-expressed nucleolin in cancer and tumor endothelial cells.
- Authors
Lam, Phoebe Y.H.; Hillyar, Christopher R.T.; Able, Sarah; Vallis, Katherine A.
- 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.
- Subjects
ENDOTHELIAL cells; NUCLEOLIN; NEOVASCULARIZATION; CANCER treatment; VASCULAR endothelial growth factors
- Publication
Journal of Labelled Compounds & Radiopharmaceuticals, 2016, Vol 59, Issue 12, p492
- ISSN
0362-4803
- Publication type
Article
- DOI
10.1002/jlcr.3439