期刊
MOLECULAR PHARMACEUTICS
卷 13, 期 1, 页码 180-189出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.5b00630
关键词
necrosis; targeted radionuclide therapy; skyrin; I-131; SPECT/CT; cancer
资金
- National Natural Science Foundation of China [81473120]
- Ninth Batch of Six Talent Peaks Project of Jiangsu Province [2012-YY-008]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
An innovative anticancer approach targeted to necrotic tissues, which serves as a noncancerous and generic anchor, may present a breakthrough. Necrosis avid agents with a flat conjugate aromatic structure selectively accumulate in necrotic tissues, but they easily form aggregates that undesirably distribute to normal tissues. In this study, skyrin, a dianthraquinone compound with smaller and distorted pi-cores and thus decreased aggregates as compared with hypericin (Hyp), was designed to target necrosis for tumor therapy. Aggregation studies of skyrin by UV/vis spectroscopy showed a smaller selfassociation constant with skyrin than with Hyp. Skyrin was labeled by iodine-131 with a radiochemical purity of 98% and exhibited good stability in rat serum for 72 h. In vitro cell uptake studies showed significant difference in the uptake of I-131-skyrin by necrotic cells compared to normal cells (P < 0.05). Compared in rats with liver and muscle necrosis, radiobiodistribution, whole-body autoradiography, and SPECT/CT studies revealed higher accumulation of I-131-skyrin in necrotic liver and muscle (p < 0.05), but lower uptake in normal organs, relative to that of I-131-Hyp. In mice bearing H22 tumor xenografts treated with combretastatin A4 disodium phosphate, the highest uptake of I-131-skyrin was found in necrotic tumor. In conclusion, I-131-skyrin appears a promising agent with reduced accumulation in nontarget organs for targeted radionuclide therapy of solid tumors.
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