Uptake of 18F-dipicolylamine derivatives in cells infected with influenza virus

Objectives Previous studies have demonstrated that bis(Zn-dipicolylamine (DPA)) ligands exhibit high affinity for anionic phosphatidylserine (PS), which is elevated on the apoptotic cell surfaces. Cy7-DPA is an optical imaging agent for apoptosis that can be developed as a dual label tracer if labeled with 18F. The aim of this study was to evaluate the cellular uptake of these two DPA analogs (DPA and Cy7-DPA) labeled with three different linkers (18F-SFB, 18F-NFP and 18F-Al) in cells infected with pandemic 2009 H1N1 influenza virus.

Methods DPA and Cy7-DPA were labeled with N-succinimidyl 4-18F-fluorobenzoate (18F-SFB), Nitrophenyl 18F-fluoropropionate (18F-NFP) and 18F-Al respectively. A549 cells were seeded into each well for 48 h. Cell apoptosis was induced with the H1N1 virus, A/KY/180/10 (KY/180) at a multiplicity of infection of 3.0 for 0, 24, and 48 hr respectively prior to the addition of tracer. Three µCi of each tracer was then added to each well and incubated at 37 0C for 1 h (n=4). Uptake was calculated by % (counts in cells)/total counts.

Results As shown in the table below, regardless of the linkers and tracers used, the uptake for the infected groups was significantly higher than that of the control (p<0.05), with 3.4 and 1.5 fold higher for 18F-SFB and 18F-NFP linkers, and 1.5 for DPA and 5.6 for Cy7-DPA labeled with 18F-Al, respectively. The highest uptake was obtained with the 18F-SFB linker (~19%), but the highest ratio was with 18F-Al-Cy7-DPA.

Conclusions The uptake was largely influenced by the choice of the linker and was consistently higher for the 18F-SFB linker, but 18F-Al-Cy7-DPA holds greater potential because of its capability in dual label imaging.