title: Necrosis affinity evaluation of 131I-hypericin in a rat model of induced necrosis.
abstract: Cancers are often with spontaneous or therapeutic necrosis that could be utilized as a generic target for developing new treatments. The purpose of this study was to investigate the biodistribution and pharmacokinetics of radioiodinated hypericin (Hyp), a naturally occurring compound, after intravenous (i.v.) injection in a rat model of liver and muscle necrosis (n = 42), and evaluate its necrosis affinity. Hyp was labeled with (131)I with labeling efficiency >99%. After incubating in solution/rat plasma for 8 days, radiochemical purity of (131)I-Hyp remained 98.1 and 97.1%, respectively, indicating good in vitro stability. SPECT-CT images at 24 h after i.v. injection of (131)I-Hyp in rats with induced liver and muscle necrosis showed obvious tracer absorption in necrotic tissues. Biodistribution studies revealed that the percentage of the injected dose per gram of tissue (%ID/g) evolved from 1.9 %ID/g at 6 h, through a maximum 3.0 %ID/g at 12 h, to 1.0 %ID/g at 192 h in necrotic liver. Pharmacokinetics studies revealed that the terminal elimination half-life, total body clearance and area under the curve of (131)I-Hyp were 32.7 h, 9.2 L/h/kg and 1.6 MBq/L*h, respectively. These results demonstrated that (131)I-Hyp features a long blood circulation in animals and persistent retention in necrotic tissues. Therefore, (131)I-labeled Hyp could be a broad-spectrum anti-tumor agent with a cost much cheaper relative to the biological agents such as monoclonal antibodies.
authors.affiliation: Lab of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Kong
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Cuihua
authors.initials: C
authors.lastname: Jiang
authors.forename: Xiao
authors.initials: X
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: Dejian
authors.initials: D
authors.lastname: Huang
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Wang
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Fang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Ziping
authors.initials: Z
authors.lastname: Sun
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
mesh_terms: D000818:Animals; D000873:Anthracenes; D019540:Area Under Curve; D006207:Half-Life; D007456:Iodine Isotopes / Q000008:administration & dosage* / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D009336:Necrosis / Q000188:drug therapy* / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D000873:Anthracenes; D007456:Iodine Isotopes; D019275:Radiopharmaceuticals; D010569:Perylene; C004965:hypericin