'Royal College of Obstetricians & Gynaecologists (RCOG)'
Abstract
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
