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. ¹³¹I labeled necrosis-avid agent protohypericin (¹³¹I-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 ¹³¹I-prohy with and without combined CA4P (3.87 ± 0.38 and 2.96 ± 0.34%ID/g). ¹³¹I-prohy + CA4P enhanced the uptake of ¹³¹I-prohy in necrotic tumor compared to ¹³¹I-prohy alone. The TNTR combined with CA4P prolonged survival of tumor bearing mice relative to vehicle control group, CA4P control group and ¹³¹I-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.