Efficient bioconjugation of 5-fluoro-5-deoxy-ribose (FDR) to RGD peptides for positron emission tomography (PET) imaging of v3 integrin receptorElectronic supplementary information (ESI) available: Experimental methods and crystallographic data. See DOI: 10.1039/c3ob40550h

• Main Authors: Dall'Angelo, Sergio, Zhang, Qingzhi, Fleming, Ian N, Piras, Monica, Schweiger, Lutz F, O'Hagan, David, Zanda, Matteo
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c3ob40550h

The utility of 5-fluoro-5-deoxyribose (FDR) as an efficient bioconjugation agent for radiolabelling of the RGD peptides c(RGDfK) and c(RGDfC) is demonstrated. The bioconjugation is significantly superior to that achieved with 2-fluoro-2-deoxyglucose (FDG) and benefits from the location of the fluorine at C-5, and that ribose is a 5-membered ring sugar rather than a 6-membered ring. Both features favour ring opening to the aldehydic form of the sugar to promote smooth oxime ligation with aminooxy ether functionalised peptides. [ 18 F]FDR was prepared in this study by synthesis from fluoride-18 using an automated synthesis protocol adapting that used routinely for [ 18 F]FDG. c(RGDfK) was functionalised with an aminooxyacetyl group (Aoa) via its lysine terminus, while c(RGDfC) was functionalised with an aminooxyhexylmaleimide (Ahm) through a cysteinemaleimide conjugation. Bioconjugation of [ 18 F]FDR to c(RGDfC)-Ahm proved to be more efficient than c(RGDfK)-Aoa (92% versus 65%). The unlabelled ( 19 F) bioconjugates c(RGDfK)-Aoa-FDR and c(RGDfC)-Ahm-FDR were prepared and their in vitro affinity to purified integrin v 3 was determined. c(RGDfK)-Aoa-FDR showed the greater affinity. Purified hot bioconjugates c(RGDfK)-Aoa-[ 18 F]FDR and c(RGDfC)-Ahm-[ 18 F]FDR were assayed by incubation with MCF7, LNCaP and PC3 cell lines. In both cases the conjugated RGD peptides showed selectivity for PC3 cells, which express v 3 integrin, with the c(RGDfK)-Aoa-[ 18 F]FDR demonstrating better binding, consistent with its higher in vitro affinity. The study demonstrates that [ 18 F]FDR is an efficient bioconjugation ligand for RGD bioactive peptides. [ 18 F]-5-Fluoro-5-deoxyribose ([ 18 F]FDR) is shown to be an efficient conjugation agent for radiolabelling of the RGD peptides with the fluorine-18 isotope.