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 ¹³¹I-Hyp in rat necrosis models. Hyp solubility in NaCh solutions was evaluated by equilibrium solubility measurement. Biodistribution of ¹³¹I-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 ¹³¹I-Hyp in NaCh solutions was studied in healthy rats. Results showed NaCh could improve Hyp solubility and ¹³¹I-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_1/2z (11.93, 8.96 h, p > 0.05) and AUC (0–∞) (421.21, 553.34 MBq/L h, p < 0.05) of ¹³¹I-Hyp in 2, 60 mmol/L of NaCh solutions, respectively. In conclusion, NaCh was an effective cosolvent, and the necrosis avidity of NaCh-dissolved ¹³¹I-Hyp/Hyp was demonstrated.

Keywords:

• Necrosis targeting
• pharmacokinetics
• radiobiodistribution
• sodium cholate
• solubility
• SPECT/CT scanning

Acknowledgements

We thank Mr Changwen Fu and Mr Yu Fu, Department of Nuclear Medicine, the First Affiliated Hospital of Nanjing Medical University, for their wonderful work in SPECT-CT scanning.