Abstract
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 18F-FBEM. 18F-FBEM was synthesized by coupling 18F-fluorobenzoic acid (18F-FBA) with N-(2-aminoethyl)maleimide using optimized reaction conditions. The yield of 18F-FBEM-Cys-Annexin V was 71.5% ± 2.0% (n = 4, based on the starting 18F-FBEM, non-decay corrected). The radiochemical purity of 18F-FBEM-Cys-Annexin V was >95%. The specific radioactivities of 18F-FBEM and 18F-FBEM-Cys-Annexin V were >150 and 3.17 GBq/µmol, respectively. Like the 1st generation 18F-SFB-Annexin V, the novel 18F-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 18F-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 18F-FBEM-Cys-Annexin V is a potential apoptosis imaging agent.
Highlights
Apoptosis plays an important role, in physiology and in pathology [1,2]
We report the labeling and preliminary in vivo evaluation of the novel 18F-FBEM-Cys-Annexin V in normal mice and in rat models of apoptosis induced by cycloheximide
According to high-performance liquid chromatography (HPLC) analysis, the radiochemical purity of 18F-FBEM-Cys-Annexin V was above 95%
Summary
Apoptosis plays an important role, in physiology and in pathology [1,2]. The anticoagulant activity is based on the high-affinity for PS These characteristics make annexin V derivatives suitable candidates for imaging of apoptosis. Tc(CO)3-HIS-cys-Anx V [12], 99mTc-annexin V-117 [13] and 99mTc-His10-annexin V [14] These new annexin V molecules labeled by site-specific methods greatly improve sensitivity for detecting cell death in vivo [15]. Our group has reported a site-specific 99mTc labeling method of a novel annexin V derivative (Cys-Annexin V) with a single cysteine residue at C-terminal [16]. Some groups have reported the labeling of annexin V with N-succinimidy-4-18F-fluorobenzoate (18F-SFB) for PET imaging of apoptosis [17,18,19], this labeling method is non-specific, as the. Apoptosis was confirmed in situ on liver slices using the terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay
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