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Oncotarget. 2015 Sep 22;6(28):26400-10. doi: 10.18632/oncotarget.4568.

Tumor necrosis targeted radiotherapy of non-small cell lung cancer using radioiodinated protohypericin in a mouse model.

Author information

1
Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
2
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, P.R.China.
3
Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, P.R.China.
4
Shandong Academy of Medical Sciences, Jinan 250062, Shandong, P.R.China.
5
Theragnostic Laboratory, Campus Gasthuisberg, KU Leuven, 3000 Leuven, Belgium.

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.

KEYWORDS:

drug combination; necrosis-avid agent; protohypericin; radiopharmaceutical; tumor necrosis targeted radiotherapy

PMID:
26305548
PMCID:
PMC4694910
DOI:
10.18632/oncotarget.4568
[Indexed for MEDLINE]
Free PMC Article

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