title: Preliminary biological evaluation of ¹⁸F-FBEM-Cys-Annexin V a novel apoptosis imaging agent.
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.
authors: Ministry of Health & Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. luchunxiong@jsinm.org.
authors: Chunxiong
authors: C
authors: Lu
authors: Ministry of Health & Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. jiangquanfu@jsinm.org.
authors: Quanfu
authors: Q
authors: Jiang
authors: Jiangsu Target Pharma Laboratories Inc., Changzhou High-Tech Research Institute of Nanjing University, Changzhou 213164, China. huminj98@163.com.
authors: Minjin
authors: M
authors: Hu
authors: Ministry of Health & Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. tangcheng@jsinm.org.
authors: Cheng
authors: C
authors: Tan
authors: Ministry of Health & Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. yuhuixin@jsinm.org.
authors: Huixin
authors: H
authors: Yu
authors: Jiangsu Target Pharma Laboratories Inc., Changzhou High-Tech Research Institute of Nanjing University, Changzhou 213164, China. huazc@nju.edu.cn.|The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China. huazc@nju.edu.cn.
authors: Zichun
authors: Z
authors: Hua
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000737:chemistry* / Q000378:metabolism*; D017209:Apoptosis; D003545:Cysteine / Q000737:chemistry; D065669:Hepatobiliary Elimination; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D008301:Maleimides / Q000737:chemistry; D051379:Mice; D023421:Models, Animal; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000378:metabolism*; D051381:Rats
chemical_list: D017304:Annexin A5; D008301:Maleimides; C512447:N-(2-(4-18F-fluorobenzamido)ethyl)maleimide; D019275:Radiopharmaceuticals; D003545:Cysteine