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

Journal article

Surface overexpression of nucleolin provides an anchor for specific attachment of biomolecules to cancer and angiogenic endothelial cells. The peptide F3 is a high affinity ligand of the nucleolin receptor (NR) thathas been investigated as a carrier to deliver biologically active molecules to tumors for both therapeutic and imaging applications. A site-specifically PEGylated F3 derivative was radiolabeled with [18F] AlF3. Binding affinity and cellular distribution ofthe compound was assessed in tumor (H2N) and tumor endothelial (2H-11) cells. Specific uptake via the NR was demonstrated by siRNA knockdown of nucleolin in both cell lines. Partition and plasma stability of the compound were assessed at 37°C. 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. SiRNA knockdown of nucleolin resulted in a binding affinity reduction of 50-60 %, 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 potentialas a tumor and angiogenesis tracer.

Authors: Vallis, K; Lam, P; Able, S; Hillyar, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Journal of Labelled Compounds and Radiopharmaceuticals
• Publication date: 2016-09-04
• ISSN: 1099-1344
• Keywords: endothelial cells; F3; nucleolin receptor; transglutaminase; [18F]Al-F