Excretion and toxicity evaluation of131I-Sennoside A as a necrosis-avid agent.
1. Sennoside A (SA) is a newly identified necrosis-avid agent that shows capability for imaging diagnosis and tumor necrosis targeted radiotherapy. As a water-soluble compound,131I-Sennoside A (131I-SA) might be excreted predominately through the kidneys with the possibility of nephrotoxicity. 2. To further verify excretion pathway and examine nephrotoxicity of131I-SA, excretion and nephrotoxicity were appraised. The pharmacokinetics, hepatotoxicity and hematotoxicity of131I-SA were also evaluated to accelerate its possible clinical translation. All these studies were conducted in mice with ethanol-induced muscular necrosis following a single intravenous administration of 131I-SA at 18.5 MBq/kg or 370 MBq/kg. 3. Excretion data revealed that131I-SA was predominately (73.5% of the injected dose (% ID)) excreted via the kidneys with 69.5% ID detected in urine within 72 h post injection. Biodistribution study indicated that131I-SA exhibited initial high distribution in the kidneys but subsequently a fast renal clearance, which was further confirmed by the results of autoradiography and single-photon emission computed tomography-computed tomography (SPECT-CT) imaging. The maximum necrotic to normal muscle ratio reached to 7.9-fold at 48 h post injection, which further verified the necrosis avidity of131I-SA. Pharmacokinetic parameters showed that131I-SA had fast blood clearance with an elimination half-life of 6.7 h. Various functional indexes were no significant difference (p > 0.05) between before administration and 1 d, 8 d, 16 d after administration. Histopathology showed no signs of tissue damage. 4. These data suggest131I-SA is a safe and promising necrosis-avid agent applicable in imaging diagnosis and tumor necrosis targeted radiotherapy.
a Department of Natural Medicinal Chemistry & Jiangsu Key Laboratory of Drug Screening , China Pharmaceutical University , Nanjing , Jiangsu Province , P.R. China.
Zhiqi
Z
Yin
a Department of Natural Medicinal Chemistry & Jiangsu Key Laboratory of Drug Screening , China Pharmaceutical University , Nanjing , Jiangsu Province , P.R. China.|b Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu Province , P.R. China.|c Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing , Jiangsu Province , P.R. China.
Lidan
L
Sun
b Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu Province , P.R. China.|c Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing , Jiangsu Province , P.R. China.
Qiaomei
Q
Jin
d Department of Nuclear Medicine , Renji Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai , P.R. China.
Shaoli
S
Song
b Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu Province , P.R. China.|c Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing , Jiangsu Province , P.R. China.|e Department of Radiology , Faculty of Medicine, K.U. Leuven , Leuven , Belgium , and.
Yuanbo
Y
Feng
a Department of Natural Medicinal Chemistry & Jiangsu Key Laboratory of Drug Screening , China Pharmaceutical University , Nanjing , Jiangsu Province , P.R. China.
Hong
H
Liao
b Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu Province , P.R. China.|c Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing , Jiangsu Province , P.R. China.|e Department of Radiology , Faculty of Medicine, K.U. Leuven , Leuven , Belgium , and.
Yicheng
Y
Ni
b Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu Province , P.R. China.|c Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing , Jiangsu Province , P.R. China.
Jian
J
Zhang
f Department of Nuclear Medicine , The First Affiliated Hospital of Nanjing Medical University , Nanjing , Jiangsu Province , P.R. China.
Wei
W
Liu
D000818:Animals; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D009336:Necrosis; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000633:toxicity*; D012676:Senna Extract / Q000378:metabolism / Q000633:toxicity*; D000081226:Sennosides; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D000081226:Sennosides; D012676:Senna Extract
131I-Sennoside A; excretion; necrosis-avid agent; toxicity evaluation