Radioiodinated hypericin: its biodistribution, necrosis avidity and therapeutic efficacy are influenced by formulation.

Abstract

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 ((123)I-Hyp and (131)I-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. (123)I-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 cm(3) with high radioactivity (3.1 ± 0.3% ID/g) were detected 6 days post-treatment. By contrast, (131)I-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 cm(3) 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.

• Authors: Marlein Miranda Cona, Yeranddy Aguiar Alpizar, Junjie Li, Matthias Bauwens, Yuanbo Feng, Ziping Sun, Jian Zhang, Feng Chen, Karel Talavera, Peter de Witte, Alfons Verbruggen, Raymond Oyen, Yicheng Ni
• Journal: Pharmaceutical research (Pharm Res) Vol. 31 Issue 2 Pg. 278-90 (Feb 2014) ISSN: 1573-904X [Electronic] United States
• PMID: 23934256 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracenes
• Antineoplastic Agents
• Iodine Radioisotopes
• Radiopharmaceuticals
• Water
• Polyethylene Glycols
• Perylene
• hypericin
• Dimethyl Sulfoxide

Topics

• Animals
• Anthracenes
• Antineoplastic Agents (chemistry, metabolism, pharmacology)
• Chemistry, Pharmaceutical (methods)
• Dimethyl Sulfoxide (chemistry)
• Iodine Radioisotopes (chemistry, metabolism, pharmacology)
• Liver (metabolism)
• Male
• Necrosis
• Neoplasms (drug therapy, metabolism)
• Perylene (analogs & derivatives, chemistry, metabolism, pharmacology)
• Polyethylene Glycols (chemistry)
• Radiopharmaceuticals (chemistry, metabolism, pharmacology)
• Rats
• Spleen (metabolism)
• Tissue Distribution
• Water (chemistry)