Radiopharmaceutical evaluation of ¹³¹I-protohypericin as a necrosis avid compound

Abstract

Hypericin is a necrosis avid agent useful for nuclear imaging and tumor therapy. Protohypericin, with a similar structure to hypericin except poorer planarity, is the precursor of hypericin. In this study, we aimed to investigate the impact of this structural difference on self-assembly, and evaluate the necrosis affinity and metabolism in the rat model of reperfused hepatic infarction. Protohypericin appeared less aggregative in solution compared with hypericin by fluorescence analysis. Biodistribution data of ¹³¹I-protohypericin showed the percentage of injected dose per gram of tissues (%ID/g) increased with time and reached to the maximum of 7.03 at 24 h in necrotic liver by gamma counting. The maximum ratio of target/non-target tissues was 11.7-fold in necrotic liver at 72 h. Pharmacokinetic parameters revealed that the half-life of ¹³¹I-protohypericin was 14.9 h, enabling a long blood circulation and constant retention in necrotic regions. SPECT-CT, autoradiography, and histological staining showed high uptake of ¹³¹I-protohypericin in necrotic tissues. These results suggest that ¹³¹I-protohypericin is a promising necrosis avid compound with a weaker aggregation tendency compared with hypericin and it may have a broad application in imaging and oncotherapy.

• Aggregation
• biodistribution
• necrosis affinity
• pharmacokinetics
• protohypericin

Acknowledgements

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

Declaration of interest

This work was partially supported by the National Natural Science Foundation of China (No. 81473120), the 333 project in Jiangsu Province (BRA2012211), the Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (No. ZJ11175), and sponsored by the Ninth Batch of “Six Talent Peaks” Project of Jiangsu Province (No. 2012-YY-008). The authors declare no competing financial interest. The authors alone are responsible for the content and writing of this article.

Supplementary material available online

Supplementary Figures S1-S4.