International journal of oncology

Biodistribution and radiation dosimetry of radioiodinated hypericin as a cancer therapeutic.

PMID 24366374


Iodine-131‑labeled monoiodohypericin (131I‑Hyp) is a necrosis avid compound used as a complementary anticancer agent. Herein, the biodistribution in rats with re-perfused partial liver infarction (RPLI) was used to estimate its human internal radiation dosimetry. Iodine-123‑labeled monoiodohypericin (123I-Hyp) as a safer surrogate for 131I-Hyp was prepared with iodogen as oxidant. Determination of radiochemical yield and purification was performed by high performance liquid chromatography (HPLC). To control aggregation, the formulation was macroscopically and microscopically examined. Biodistribution of 123I-Hyp was studied in RPLIxa0rats (n=18) at 4, 24 and 48xa0h post-injection. Tissue gamma counting (TGC), autoradiography and histology were performed. Dosimetry of 131I-Hyp in hepatic necrosis and in normal human organs was estimated using biodistribution data of 123I-Hyp, the Organ Level Internal Dose Assessment/Exponential Modeling (OLINDA/EXM®), a sphere model and male and female phantoms. A radiochemical yield of 95% was achieved in labeling of 123I-Hyp with a radiochemical purity of 99% after HPLC purification. In the Hyp added formulation, no macroscopic but minimal microscopic aggregation was observed. By TGC, selective accumulation in hepatic infarction and low uptake in viable liver of 123I‑Hyp/Hyp were detected, as confirmed by autoradiography and histology. Significantly higher doses of 131I-Hyp were delivered to necrotic (276‑93,600xa0mGy/MBq) than to viable (4.2xa0mGy/MBq) liver (P<0.05). In normal organs, 123I‑Hyp was eliminated within 24xa0h except for relatively high levels in the lungs and thyroid. Hepatobiliary elimination was a major pathway of 123I-Hyp causing high activity in the intestines. For both genders, dosimetry showed the longest residence time of 131I-Hyp in the remainder, followed by the lungs, intestines and thyroid. The highest absorbed radiation dose was seen in necrotic tissues and the shortest residence times and lowest absorbed radiation dose were found in the brain. 131I-Hyp selectively delivers higher radiation dose to necrosis compared with the rest of the body. Among normal organs, thyroids, lungs and intestines receive considerable radiation dose, which deserves cautious attention in developing this anticancer approach.