Experimental evaluation of radioiodinated sennoside B as a necrosis-avid tracer agent

Abstract

Necrosis-avid agents are a class of compounds that selectively accumulate in the necrotic tissues after systemic administration, which can be used for in vivo necrosis imaging and targeted therapies. In order to search for a necrosis-avid tracer agent with improved drugability, we labelled iodine-131 on sennoside B (SB) as a naturally occurring median dianthrone compound. The necrosis targetability and clearance properties of ¹³¹I-SB were evaluated in model rats with liver and muscle necrosis. On SPECT/CT images, a “hot spot” in the infarcted liver lobe and necrotic muscle was persistently observed at 24 h and 72 h post-injection (p.i.). Gamma counting of the tissues of interest revealed a radioactivity ratio of necrotic to viable liver at 4.6 and 3.4 and of necrotic to viable muscle at 7.0 and 8.8 at 24 h and 72 h p.i., respectively. The good match of autoradiographs and fluoromicroscopic images with corresponding histochemical staining suggested preferential uptake of ¹³¹I-SB in necrotic tissue. Pharmacokinetic study revealed that ¹³¹I-SB has an elimination half-life of 8.6 h. This study indicates that ¹³¹I-SB shows not only prominent necrosis avidity but also favourable pharmacokinetics, which may serve as a potential necrosis-avid diagnostic agent for assessment of tissue viability.

• Autoradiography
• biodistribution
• necrosis targeting
• pharmacokinetics
• radioiodine
• sennoside B
• SPECT imaging

Acknowledgements

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

This work was partially supported by the National Natural Science Foundation of China (No. 81473120), 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, the Ninth Batch of “Six Talent Peaks” Project of Jiangsu Province (No. 2012-YY-008), and the Laboratory platform construction about the protection and utilization of traditional Chinese medicine resources (No. Bijie Municipal Science and technology achievement transformation project [2014] No. 8).