Radioiodinated Hypericin: Its Biodistribution, Necrosis Avidity and Therapeutic Efficacy are Influenced by Formulation

Purpose

To study whether formulation influences biodistribution, necrosis avidity and tumoricidal effects of the radioiodinated hypericin, a necrosis avid agent for a dual-targeting anticancer radiotherapy.

Methods

Iodine-123- and 131-labeled hypericin (¹²³I-Hyp and ¹³¹I-Hyp) were prepared with Iodogen as oxidant, and formulated in dimethyl sulfoxide (DMSO)/PEG400 (polyethylene glycol 400)/water (25/60/15, v/v/v) or DMSO/saline (20:80, v/v). The formulations with excessive Hyp were optically characterized. Biodistribution, necrosis avidity and tumoricidal effects were studied in rats (n?=?42) without and with reperfused liver infarction and implanted rhabdomyosarcomas (R1). To induce tumor necrosis, R1-rats were pre-treated with a vascular disrupting agent. Magnetic resonance imaging, tissue-gamma counting, autoradiography and histology were used.

Results

The two formulations differed significantly in fluorescence and precipitation. ¹²³I-Hyp/Hyp in DMSO/PEG400/water exhibited high uptake in necrosis but lower concentration in the lung, spleen and liver (p?<?0.01). Tumor volumes of 0.9?±?0.3 cm³ with high radioactivity (3.1?±?0.3% ID/g) were detected 6 days post-treatment. By contrast, ¹³¹I-Hyp/Hypin DMSO/saline showed low uptake in necrosis but high retention in the spleen and liver (p?<?0.01). Tumor volumes reached 2.6?±?0.7 cm³ with low tracer accumulation (0.1?±?0.04%ID/g).

Conclusions

The formulation of radioiodinated hypericin/hypericin appears crucial for its physical property, biodistribution, necrosis avidity and tumoricidal effects.