Hydroxypropyl β-cyclodextrin as the pharmaceutical excipient for radioiodinated hypericin improves solubility and plasma clearance without affecting netrotic targeting.

Objectives: ¹³¹I-Hyp serves a powerful radiopharmaceutical against solid tumours when it was concomitantly used with a vascular disrupting agent (VDA), which was named as the sequential dual-targeting theragnostic strategy (SDTTS) or Oncocidia. However, poor hydrophilicity of both Hypand ¹³¹I-Hyp has always been an obstacle for its clinical application. We were committed to finding a legal preparation (Hydroxypropyl β-cyclodextrin, HP-β-CD) for ¹³¹I-Hyp/Hyp to replace their traditional preparation (with lots of DMSO) for intravenous injection. Materials and Methods: solubility of Hyp in HP-β-CD solution was evaluated by UV spectrophotometry and 50% HP-β-CD was chosen as the main solvent. ¹³¹I-Hyp was labelled from 1 mg/mL Hyp in the traditional preparation (contained 30% DMSO), the improved preparation 1 (contained 50% HP-β-CD), and the improved preparation 2 (contained 6% DMSO with 50% HP-β-CD) , i.v. injected at the dosage of 3.96 MBq/kg of ¹³¹I in rats (N=6/group) with liver and muscle necrosis. Tissues were sampled after 24 hr for gamma counting, autoradiography and H&E staining.

Results: No preparation was be labelled with ¹³¹I, and ¹³¹I-Hyp exhibited radiochemical purity above 90% in the preparations. Hyp solubility was enhanced with increasing HP-β-CD, and higher than 1 mg/mL in the solvents higher than 40% HP-β-CD. The targetability of ¹³¹I-Hyp did not changed in the improved preparations, necrotic liver exhibited higher radioactivity, blue-stained by EB and lower hematoxylin dye on H&E staining. The radioactivity cleaned fast in blood in the improved preparations.

Conclusions: The improved preparations contained HP-β-CD could be a suitable pharmaceutical excipient for i.v. injection of ¹³¹I-Hyp solution.