We sought to reduce the radioactive intestinal waste after intravenous injection of necrosis avid iodine-131-labeled hypericin in dual-targeting anticancer radiotherapy and to study its pharmacokinetics in rats using a newly designed catheter. Iodine-123-labeled hypericin was prepared with iodogen as oxidant and characterized by high-performance liquid chromatography and mass spectrometry. After iodine-123-labeled hypericin administration, duodenal juice was collected via a catheter from groups of rats (n = 5) at intervals of 0–4, 4–8 or 20–24 h. The content was assessed by gamma-counting. The biodistribution and pharmacokinetics of iodine-123-labeled hypericin were investigated in rats without (n = 5) and with continuous catheterization (n = 5) for 9 h. After labeling, a high radiochemical yield was obtained with iodine-123-labeled hypericin (>95%), as confirmed by high-performance liquid chromatography and mass spectrometry. In the duodenal aspirate from animals with intermittent catheterization during 24 h, radioactivity accounted for 46% of the total with two peaks at 3 h and 8 h, suggesting enterohepatic circulation. Rats with 9 h of catheterization exhibited one peak representing 20% of the radioactivity. Major metabolites appeared to be conjugated iodine-123-labeled hypericin forms. In rats without and with catheter, iodine-123-labeled hypericin showed exponential elimination from plasma with no significant dehalogenation. Delayed iodine-123-labeled hypericin excretion, a higher maximum concentration (C_max), larger area under concentration-time curve [AUC_(0-∞)] and a longer mean residence time were observed in non-catheterized animals (P < 0.05). The catheterized group exhibited lower urinary excretion than non-catheterized group (P < 0.05). Rats with a catheter showed lower radioactivity (P = 0.01) in the small intestines than those without a catheter (1.82 ± 0.41 versus 18.95 ± 4.32 percentage of the injected dose). After iodine-123-labeled hypericin administration, the radioactivity excreted into bile was efficiently removed from the body via a duodenal catheter. Radiation overexposure due to the prolonged elimination of iodine-131-labeled hypericin can be prevented using this approach.

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Improved clearance of radioiodinated hypericin as a targeted anticancer agent by using a duodenal drainage catheter in rats