Preparation and validation of cyclodextrin-based excipients for radioiodinated hypericin applied in a targeted cancer radiotherapy

Background Iodine-131 labeled hypericin (131I-Hyp) has been utilized as a necrosis-avid theragnostic tracer in a dual targeting pan-anticancer strategy called OncoCiDia. Widespread use of previously-tested solvent dimethyl sulfoxide (DMSO) is limited by safety concerns. To tackle this, the present study was designed to explore a clinically feasible excipient for the formulation of the hydrophobic 131I-Hyp for intravenous administration. Method Solubility of Hyp in serial solutions of already-approved hydroxypropyl-β-cyclodextrin (HP-β-CD) was evaluated by UVspectrophotometry and 50% HP-β-CD was chosen for further experiments. Two novel HP-β-CD-based formulations of 131I-Hyp were compared with previous DMSO-based formulation, with regards to necrosis-targetability and biodistribution, by magnetic resonance imaging, single-photon emission computed tomography (SPECT), gamma counting, autoradiography, fluorescence microscopy and histopathology. Results Hyp solubility was enhanced with increasing HP-β-CD concentrations. The radiochemical purity of 131I-Hyp was higher than 90% in all formulations. The necrosis-targetability of 131I-Hyp in the novel formulations was confirmed in vivo by SPECT and in vitro by autoradiography, fluorescence microscopy and histopathology. The plasma clearance of radioactivity was faster in the novel formulations. Conclusion The novel 131I-Hyp formulations with HP-β-CD could be a suitable pharmaceutical excipient for 131I-Hyp for intravenous administration.