Preliminary Biological Evaluation of (18)F-FBEM-Cys-Annexin V a Novel Apoptosis Imaging Agent

A novel annexin V derivative (Cys-Annexin V) with a single cysteine residue at its C-terminal has been developed and successfully labeled site-specifically with (18)F-FBEM. (18)F-FBEM was synthesized by coupling (18)F-fluorobenzoic acid ((18)F-FBA) with N-(2-aminoethyl)maleimide using optimized reaction conditions. The yield of (18)F-FBEM-Cys-Annexin V was 71.5% ± 2.0% (n = 4, based on the starting (18)F-FBEM, non-decay corrected). The radiochemical purity of (18)F-FBEM-Cys-Annexin V was >95%. The specific radioactivities of (18)F-FBEM and (18)F-FBEM-Cys-Annexin V were >150 and 3.17 GBq/µmol, respectively. Like the 1st generation (18)F-SFB-Annexin V, the novel (18)F-FBEM-Cys-Annexin V mainly shows renal and to a lesser extent, hepatobiliary excretion in normal mice. In rat hepatic apoptosis models a 3.88 ± 0.05 (n = 4, 1 h) and 10.35 ± 0.08 (n = 4, 2 h) increase in hepatic uptake of (18)F-FBEM-Cys-Annexin V compared to normal rats was observed after injection via the tail vein. The liver uptake ratio (treated/control) at 2 h p.i. as measured via microPET correlated with the ratio of apoptotic nuclei in liver observed using TUNEL histochemistry, indicating that the novel (18)F-FBEM-Cys-Annexin V is a potential apoptosis imaging agent.