title: Improvement of solubility and targetability of radioiodinated hypericin by using sodium cholate based solvent in rat models of necrosis.
abstract: Hypericin (Hyp) is newly recognized as a necrosis avid agent, but its poor solubility imposes a great hindrance in clinical application. The aim of this paper was to explore sodium cholate (NaCh) as a potential solvent for Hyp and assess the targetability of (131)I-Hyp in rat necrosis models. Hyp solubility in NaCh solutions was evaluated by equilibrium solubility measurement. Biodistribution of (131)I-Hyp in NaCh solutions and mixed organic solvents was investigated in rat models of liver and muscle necrosis examined with MRI and SPECT/CT in vivo. In addition, pharmacokinetics of (131)I-Hyp in NaCh solutions was studied in healthy rats. Results showed NaCh could improve Hyp solubility and (131)I-Hyp incubated in NaCh solutions/rat plasma was stable up to 120 h. On SPECT/CT images at 24 h post injection, liver infarction location appeared as hot spots. Liver necrosis-to-liver ratios were 12.2, 10.0, 9.6 and 8.2 in 60, 15, 2 mmol/L of NaCh solutions and organic solvents, and muscle necrosis-to-liver ratios were 11.1, 10.1, 7.7 and 7.4, respectively. Pharmacokinetics study revealed t(1/2)z (11.93, 8.96 h, p > 0.05) and AUC (0-∞) (421.21, 553.34 MBq/L h, p < 0.05) of (131)I-Hyp in 2, 60 mmol/L of NaCh solutions, respectively. In conclusion, NaCh was an effective cosolvent, and the necrosis avidity of NaCh-dissolved (131)I-Hyp/Hyp was demonstrated.
authors: Department of Natural Medicinal Chemistry, China Pharmaceutical University , Nanjing, Jiangsu Province , P.R. China .
authors: Yun
authors: Y
authors: Ji
authors: Ying
authors: Y
authors: Zhan
authors: Cuihua
authors: C
authors: Jiang
authors: Xiao
authors: X
authors: Jiang
authors: Meng
authors: M
authors: Gao
authors: Wei
authors: W
authors: Liu
authors: Yue
authors: Y
authors: Li
authors: Junhu
authors: J
authors: Wang
authors: Qingqing
authors: Q
authors: Wang
authors: Marlein Miranda
authors: MM
authors: Cona
authors: Nan
authors: N
authors: Yao
authors: Xiaoning
authors: X
authors: Wang
authors: Zhijun
authors: Z
authors: Fang
authors: Zhiqi
authors: Z
authors: Yin
authors: Jian
authors: J
authors: Zhang
authors: Ziping
authors: Z
authors: Sun
authors: Yicheng
authors: Y
authors: Ni
mesh_terms: D000818:Animals; D000873:Anthracenes; D004195:Disease Models, Animal; D007457:Iodine Radioisotopes; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009336:Necrosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D020358:Sodium Cholate / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000873:Anthracenes; D007457:Iodine Radioisotopes; D012997:Solvents; D010569:Perylene; C004965:hypericin; D020358:Sodium Cholate