title: Experimental evaluation of radioiodinated sennoside B as a necrosis-avid tracer agent.
abstract: Necrosis-avid agents are a class of compounds that selectively accumulate in the necrotic tissues after systemic administration, which can be used for in vivo necrosis imaging and targeted therapies. In order to search for a necrosis-avid tracer agent with improved drugability, we labelled iodine-131 on sennoside B (SB) as a naturally occurring median dianthrone compound. The necrosis targetability and clearance properties of (131)I-SB were evaluated in model rats with liver and muscle necrosis. On SPECT/CT images, a "hot spot" in the infarcted liver lobe and necrotic muscle was persistently observed at 24 h and 72 h post-injection (p.i.). Gamma counting of the tissues of interest revealed a radioactivity ratio of necrotic to viable liver at 4.6 and 3.4 and of necrotic to viable muscle at 7.0 and 8.8 at 24 h and 72 h p.i., respectively. The good match of autoradiographs and fluoromicroscopic images with corresponding histochemical staining suggested preferential uptake of (131)I-SB in necrotic tissue. Pharmacokinetic study revealed that (131)I-SB has an elimination half-life of 8.6 h. This study indicates that (131)I-SB shows not only prominent necrosis avidity but also favourable pharmacokinetics, which may serve as a potential necrosis-avid diagnostic agent for assessment of tissue viability.
authors.affiliation: Department of Natural Medicinal Chemistry, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing, Jiangsu Province , PR China .
authors.forename: Dongjian
authors.initials: D
authors.lastname: Zhang
authors.forename: Dejian
authors.initials: D
authors.lastname: Huang
authors.forename: Yun
authors.initials: Y
authors.lastname: Ji
authors.forename: Cuihua
authors.initials: C
authors.lastname: Jiang
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.forename: Nan
authors.initials: N
authors.lastname: Yao
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Liu
authors.forename: Haibo
authors.initials: H
authors.lastname: Shao
authors.forename: Su
authors.initials: S
authors.lastname: Jing
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Yin
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D005243:Feces / Q000737:chemistry; D007275:Injections, Intravenous; D007456:Iodine Isotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D008099:Liver / Q000000981:diagnostic imaging* / Q000473:pathology*; D008297:Male; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging* / Q000473:pathology*; D009336:Necrosis / Q000000981:diagnostic imaging / Q000473:pathology; D017207:Rats, Sprague-Dawley; D012676:Senna Extract / Q000008:administration & dosage / Q000493:pharmacokinetics; D000081226:Sennosides; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D007456:Iodine Isotopes; D000081226:Sennosides; D012676:Senna Extract
keywords: Autoradiography; SPECT imaging; biodistribution; necrosis targeting; pharmacokinetics; radioiodine; sennoside B