title: Improved clearance of radioiodinated hypericin as a targeted anticancer agent by using a duodenal drainage catheter in rats.
abstract: 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 (Cmax), 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.
authors.affiliation: Department of Imaging & Pathology, Faculty of Medicine, Biomedical Sciences Group, KU Leuven, Herestraat 49, Leuven, Belgium.
authors.forename: Marlein Miranda
authors.initials: MM
authors.lastname: Cona
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Feng
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
authors.forename: Raymond
authors.initials: R
authors.lastname: Oyen
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
mesh_terms: D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001826:Body Fluids / Q000737:chemistry; D001918:Brachytherapy / Q000379:methods*; D002408:Catheters, Indwelling; D059248:Chemoradiotherapy / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D004386:Duodenum; D007457:Iodine Radioisotopes / Q000032:analysis; D013058:Mass Spectrometry; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D010569:Perylene; C004965:hypericin
keywords: Iodine-123-labeled hypericin; bile; biodistribution; cancer; catheter; pharmacokinetics