Targetability and Biodistribution of Radioiodinated Hypericin: Comparison between Microdosing and Carrier-Added Preparations

Objectives: To study the effect of co-injecting unlabelled hypericin (Hyp) on biodistribution, necrosis uptake and tumour retention of iodine-123 or iodine-131 labelled hypericin (123/131I-Hyp), a necrosis avid agent for an anticancer radiotherapy. Methods: 123/131I-Hyp was prepared with Iodogen as oxidant and formulated in 0.6 μg/kg no-carrier-added (NCA) or 0.25 mg/kg unlabelled Hyp carrier-added (CA) forms using dimethyl sulfoxide/polyethylene glycol-400/propylene glycol/water (25/25/25/25% v/v/v/v), as solvent mixture. Comparisons on biodistribution and necrosis uptake of NCA and CA123I-Hyp were conducted on rats (n=24) of reperfused liver infarction (RPLI) in 48h p.i. Tumour retention of CA131I-Hyp was assessed in severe combined immunodeficiency (SCID) mice with fibrosarcoma (RIF-1) tumours (n=25) over 40 days. To cause intratumour necrosis, mice were pre-treated with a vascular disrupting agent CA4P at 10mg/kg. Tissue-gamma counting (TGC), autoradiography and histology were performed. Results: TGC revealed no significant difference in organ biodistribution between RPLI-rats injected with NCA and CA123I-Hyp, except in intestines, liver, lungs and stomach (P<0.05). Both preparations showed hepatobiliary excretion since intestines and faeces retained the most radioactivity. NCA and CA123I-Hyp exhibited high avidity and selectivity for hepatic infarction. From the day after injection onward, CA123I-Hyp showed greater target accumulation (7-11%ID/g) than 123I-Hyp alone (∼4%ID/g; P<0.05). In RIF-1-SCID mice receiving CA131I-Hyp, prolonged high retention in tumour necrosis was detected over 40 days p. i. TGC findings were confirmed by histological and autoradiographic analysis. Conclusions: The study demonstrated the co-injection of unlabelled Hyp affected necrosis uptake but almost no biodistribution of radioiodinated Hyp. Long-term high retention into tumour necrosis characterizes the carrier-added 131I-Hyp.