title: Synthesis and Evaluation of131I-Skyrin as a Necrosis Avid Agent for Potential Targeted Radionuclide Therapy of Solid Tumors.
abstract: 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 π-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 self-association 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 of131I-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 of131I-skyrin in necrotic liver and muscle (p < 0.05), but lower uptake in normal organs, relative to that of131I-Hyp. In mice bearing H22 tumor xenografts treated with combretastatin A4 disodium phosphate, the highest uptake of131I-skyrin was found in necrotic tumor. In conclusion,131I-skyrin appears a promising agent with reduced accumulation in nontarget organs for targeted radionuclide therapy of solid tumors.
authors.affiliation: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing 210009, Jiangsu Province, P. R. China.|Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing 210028, Jiangsu Province, P. R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing 210028, Jiangsu Province, P. R. China.
authors.forename: Qiaomei
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing 210028, Jiangsu Province, P. R. China.
authors.forename: Shengwei
authors.initials: S
authors.lastname: Yang
authors.affiliation: Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing 210028, Jiangsu Province, P. R. China.
authors.forename: Dongjian
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing 210028, Jiangsu Province, P. R. China.|College of Pharmacy, Nanjing University of Chinese Medicine , Nanjing 210023, Jiangsu Province, P. R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing 210009, Jiangsu Province, P. R. China.|Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing 210028, Jiangsu Province, P. R. China.
authors.forename: Jindian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University, School of Medicine , Shanghai 200127, P. R. China.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Song
authors.affiliation: Radiation Medical Institute, Shandong Academy of Medical Sciences , Jinan 250062, Shandong Province, P. R. China.
authors.forename: Ziping
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Theragnostic Laboratory, Campus Gasthuisberg, KU Leuven , 3000 Leuven, Belgium.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing 210028, Jiangsu Province, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing 210009, Jiangsu Province, P. R. China.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Yin
keywords: 131I; SPECT/CT; cancer; necrosis; skyrin; targeted radionuclide therapy