Radioiodinated hypericin: its biodistribution, necrosis avidity and therapeutic efficacy are influenced by formulation.
OBJECTIVE
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.
Department of Imaging & Pathology, Faculty of Medicine Biomedical Sciences Group, KU Leuven, Herestraat 49, Leuven, Belgium.
Marlein Miranda
MM
Cona
Yeranddy Aguiar
YA
Alpizar
Junjie
J
Li
Matthias
M
Bauwens
Yuanbo
Y
Feng
Ziping
Z
Sun
Jian
J
Zhang
Feng
F
Chen
Karel
K
Talavera
Peter
P
de Witte
Alfons
A
Verbruggen
Raymond
R
Oyen
Yicheng
Y
Ni
D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D009336:Necrosis; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D014867:Water / Q000737:chemistry
D000873:Anthracenes; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D014867:Water; D011092:Polyethylene Glycols; D010569:Perylene; C004965:hypericin; D004121:Dimethyl Sulfoxide