Biodistribution and anti-tumor efficacy of intratumorally injected necrosis-avid theranostic agent radioiodinated hypericin in rodent tumor models

Abstract

Hypericin has an excellent necrosis-specific targeting capacity; thus, we explored small-molecular tumor necrosis therapy (SMTNT) for inhibiting tumor growth in rodent tumor models. H22 and S180 tumor-bearing Kunming (KM) mice were intratumorally injected with ¹³¹I-monoiodohypericin (¹³¹I-MIH) to investigate the biodistribution of ¹³¹I-MIH as a function of time. Single-photon emission computed tomography (SPECT), autoradiography, fluorescence microscopy and hematoxylin and eosin (H&E) staining were performed to determine the intra-tumoral distribution of ¹³¹I-MIH. A therapeutic evaluation study was also performed in the tumor-bearing KM mice using saline and a positive drug as controls. Gamma counting, SPECT images, autoradiography and fluorescence microscopy and H&E staining results revealed intense retention of ¹³¹I-MIH in the necrotic tumor over 168 h and good in vivo stability of the agent. Therapy with a single dose of intra-tumoral administration of ¹³¹I-MIH caused significant tumor growth delay. A histopathological analysis of the tumors and normal organs further validated the therapeutic efficacy and limited systemic toxicity of ¹³¹I-MIH. The prolonged tumor retention and effective therapy indicated that ¹³¹I-MIH may be a promising intratumorally injected SMTNT agent.

• Autoradiography
• biodistribution
• intra-tumoral administration
• necrosis-avid theranostic agent
• radioiodinated hypericin
• small-molecular tumor necrosis therapy
• SPECT/CT imaging

Acknowledgments

We thank Mr. Changwen Fu and Mr. Yu Fu, Department of Nuclear Medicine, the First Affiliated Hospital of Nanjing Medical University, for their wonderful work in SPECT/CT scanning.

Declaration of interest

The authors report no declaration of interest. This work was partially supported by the National Natural Science Foundation of China (No.81473120, 21171092), the fourth phase of 333 projects in Jiangsu Province (BRA2012211), the Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (No. ZJ11175), the CZC Pharmaceutical and Technology Co., Ltd. Nanjing, China and the Ninth Batch of “Six Talent Peaks” Project of Jiangsu Province (No.2012-YY-008).

Supplementary information available online

Supplemental Figure S1