title: Tumor necrosis targeted radiotherapy of non-small cell lung cancer using radioiodinated protohypericin in a mouse model.
abstract: Lung cancer is the leading cause of cancer-related death. About 80% of lung cancers are non-small cell lung cancers (NSCLC). Radiotherapy is widely used in treatment of NSCLC. However, the outcome of NSCLC remains unsatisfactory. In this study, a vascular disrupting agent (VDA) combretastatin-A4-phosphate (CA4P) was used to provide massive necrosis targets. (131)I labeled necrosis-avid agent protohypericin ((131)I-prohy) was explored for therapy of NSCLC using tumor necrosis targeted radiotherapy (TNTR). Gamma counting, autoradiography, fluorescence microscopy and histopathology were used for biodistribution analysis. Magnetic resonance imaging (MRI) was used to monitor tumor volume, ratios of necrosis and tumor doubling time (DT). The biodistribution data revealed 131I-prohy was delivered efficiently to tumors. Tracer uptake peaked at 24 h in necrotic tumor of (131)I-prohy with and without combined CA4P (3.87 ± 0.38 and 2.96 ± 0.34%ID/g). (131)I-prohy + CA4P enhanced the uptake of (131)I-prohy in necrotic tumor compared to (131)I-prohy alone. The TNTR combined with CA4P prolonged survival of tumor bearing mice relative to vehicle control group, CA4P control group and (131)I-prohy control group with median survival of 35, 20, 22 and 27 days respectively. In conclusion, TNTR appeared to be effective for the treatment of NSCLC.
authors: Laboratory 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: Xuejiao
authors: X
authors: Liu
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.|Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, P.R.China.
authors: Cuihua
authors: C
authors: Jiang
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.|Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, P.R.China.
authors: Dongjian
authors: D
authors: Zhang
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors: Meng
authors: M
authors: Gao
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors: Fei
authors: F
authors: Peng
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors: Dejian
authors: D
authors: Huang
authors: Shandong Academy of Medical Sciences, Jinan 250062, Shandong, P.R.China.
authors: Ziping
authors: Z
authors: Sun
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.|Theragnostic Laboratory, Campus Gasthuisberg, KU Leuven, 3000 Leuven, Belgium.
authors: Yicheng
authors: Y
authors: Ni
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors: Jian
authors: J
authors: Zhang
authors: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, P.R.China.
authors: Zhiqi
authors: Z
authors: Yin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001345:Autoradiography; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059248:Chemoradiotherapy / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009336:Necrosis; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011859:Radiography; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013267:Stilbenes / Q000008:administration & dosage*; D014018:Tissue Distribution; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D013267:Stilbenes; C108325:protohypericin; D010569:Perylene; C058728:fosbretabulin
keywords: drug combination; necrosis-avid agent; protohypericin; radiopharmaceutical; tumor necrosis targeted radiotherapy