Skip to main content
Log in

Radiopharmaceutical study on Iodine-131-labelled hypericin in a canine model of hepatic RFA-induced coagulative necrosis

  • Diagnostic Imaging in Oncology
  • Published:
La radiologia medica Aims and scope Submit manuscript

Abstract

Purpose

Hypericin (HYP) has been found avid to necrosis in small animal studies. We sought to evaluate the tissue distribution of 131I-HYP in a large animal model and to explore the theranostic utilities of 131I-HYP after radiofrequency ablation (RFA).

Materials and methods

This animal experiment was approved by the institutional ethics committee. Twenty-five male dogs were enrolled and subjected to transabdominal hepatic RFA. 131I-HYP was prepared by an electrophilic substitution method and intravenously administered at 0.5 mCi/kg. Systemic and regional distributions of 131I-HYP were monitored dynamically by single-photon emission computed tomography/computed tomography (SPECT-CT), gamma counting, autoradiography, and fluorescent and light microscopy at different time points up to 14 days. Experimental data were quantified and statistically analysed.

Results

Most of the tissues and organs retained 131I-HYP only transiently. 131I-HYP was mainly metabolised in the liver and excreted into the bile. 131I-HYP gradually accumulated in the RFA-induced necrosis with a peak concentration occurring within 2 days and lasting over 2 weeks as visualised by in vivo SPECT-CT and ex vivo autoradiography and fluorescent microscopy, and quantified by radioactivity and fluorescence measurements. Accumulation of 131I-HYP was low in both the necrosis centre and normal liver tissue.

Conclusion

131I-HYP showed persistent high affinity to hepatic thermo-coagulative necrosis, but only a transient uptake by normal liver in dogs. Necrosis caused by RFA could be indicated by 131I-HYP on nuclear imaging, which suggests a supplementary measure for tumour detection and therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Friedman M, Mikityansky I, Kam A et al (2004) Radiofrequency ablation of cancer. Cardiovasc Intervent Radiol 27:427–434

    PubMed Central  PubMed  Google Scholar 

  2. Ni Y, Mulier S, Miao Y et al (2005) A review of the general aspects of radiofrequency ablation. Abdom Imaging 30:381–400

    Article  CAS  PubMed  Google Scholar 

  3. Guan YS, Sun L, Zhou XP et al (2004) Hepatocellular carcinoma treated with interventional procedures: CT and MRI follow-up. World J Gastroenterol 10:3543–3548

    PubMed  Google Scholar 

  4. King AD, Tse GM, Ahuja AT et al (2004) Necrosis in metastatic neck nodes: diagnostic accuracy of CT, MR imaging, and US. Radiology 230:720–726

    Article  PubMed  Google Scholar 

  5. Goldberg SN (2005) Science to practice: can we differentiate residual untreated tumor from tissue responses to heat following thermal tumor ablation? Radiology 234:317–318

    Article  PubMed  Google Scholar 

  6. Van de Putte M, Wang H, Chen F et al (2008) Hypericin as a marker for determination of tissue viability after radiofrequency ablation in a murine liver tumor model. Oncol Rep 19:927–932

    PubMed  Google Scholar 

  7. Van de Putte M, Wang H, Chen F et al (2008) Hypericin as a marker for determination of tissue viability after intratumoral ethanol injection in a murine liver tumor model. Acad Radiol 15:107–113

    Article  PubMed  Google Scholar 

  8. Fonge H, Van de Putte M, Huyghe D et al (2007) Evaluation of tumor affinity of mono-[(123I]iodohypericin and mono-[(123I]iodoprotohypericin in a mouse model with a RIF-1 tumor. Contrast Media Mol Imaging 2:113–119

    Article  CAS  PubMed  Google Scholar 

  9. Ni Y, Huyghe D, Verbeke K et al (2006) First preclinical evaluation of mono-[123I]iodohypericin as a necrosis-avid tracer agent. Eur J Nucl Med Mol Imaging 33:595–601

    Article  CAS  PubMed  Google Scholar 

  10. Van de Putte M, Marysael T, Fonge H et al (2012) Radiolabeled iodohypericin as tumor necrosis avid tracer: diagnostic and therapeutic potential. Int J Cancer 131:E129–E137

    Article  PubMed  Google Scholar 

  11. Cona MM, Koole M, Feng Y et al (2014) Biodistribution and radiation dosimetry of radioiodinated hypericin as a cancer therapeutic. Int J Oncol 44:819–829

    CAS  PubMed  Google Scholar 

  12. Song S, Xiong C, Zhou M et al (2011) Small-animal PET of tumor damage induced by photothermal ablation with 64Cu-bis-DOTA-hypericin. J Nucl Med 52:792–799

    Article  CAS  PubMed  Google Scholar 

  13. Li J, Cona MM, Chen F et al (2013) Sequential systemic administrations of combretastatin A4 Phosphate and radioiodinated hypericin exert synergistic targeted theranostic effects with prolonged survival on SCID mice carrying bifocal tumor xenografts. Theranostics 3:127–137

    Article  PubMed Central  PubMed  Google Scholar 

  14. Li J, Sun Z, Zhang J et al (2011) A dual-targeting anticancer approach: soil and seed principle. Radiology 260:799–807

    Article  PubMed  Google Scholar 

  15. Dalmo J, Rudqvist N, Spetz J et al (2012) Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2. Oncol Rep 27:174–181

    CAS  PubMed  Google Scholar 

  16. Ali SM, Olivo M (2002) Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells. Int J Oncol 21:531–540

    CAS  PubMed  Google Scholar 

  17. Ji Y, Zhan Y, Jiang C (2014) Improvement of solubility and targetability of radioiodinated hypericin by using sodium cholate based solvent in rat models of necrosis. J Drug Target 22:304–312

    Article  CAS  PubMed  Google Scholar 

  18. Schwarz RE, Smith DD (2008) Trends in local therapy for hepatocellular carcinoma and survival outcomes in the US population. Am J Surg 195:829–836

    Article  PubMed  Google Scholar 

  19. Cona MM, Feng Y, Li Y et al (2013) Comparative study of iodine-123-labeled hypericin and 99mTc-labeled hexakis [2-methoxy isobutyl isonitrile] in a rabbit model of myocardial infarction. J Cardiovasc Pharmacol 62:304–311

    Article  CAS  PubMed  Google Scholar 

  20. Fonge H, Vunckx K, Wang H et al (2008) Non-invasive detection and quantification of acute myocardial infarction in rabbits using mono-[123I]iodohypericin microSPECT. Eur Heart J 29:260–269

    Article  CAS  PubMed  Google Scholar 

  21. Cona MM, Li J, Feng Y et al (2013) Targetability and biodistribution of radioiodinated hypericin: comparison between microdosing and carrier-added preparations. Anticancer Agents Med Chem 2013 Aug 28. [Epub ahead of print]

  22. Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK (2000) Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int Immunol 12:1539–1546

  23. Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N (2000) Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 191:423–434

  24. Miranda Cona M, Koole M, Feng YB, Liu YW, Verbruggen A, Oyen R, Ni Y (2014) Biodistribution and radiation dosimetry of radioiodinated hypericin as a cancer therapeutic. Int J Oncol 44:819–829

  25. Miranda Cona M, Li JJ, Chen F, Feng YB, Sun Z, Zhang J, Chen F, Alpizar YA, Pérez KT, de Witte P, Verbruggen A, Oyen R, Ni Y (2014) Radioiodinated hypericin: its biodistribution, necrosis avidity and therapeutic efficacy are influenced by formulation. Pharm Res 31:278–290

  26. Miranda Cona M, Feng YB, Verbruggen A, Oyen R, Ni Y (2013) Improve clearance of radioiodinated hypericin as a targeted anticancer agent by using a duodenal drainage catheter in rats. Exp Biol Med 238:1437–1449

Download references

Acknowledgments

This study was partially supported by National Natural Science Foundation of China (81201169), National High Technology Research and Development Program of China (2012AA022701) and LIAONING S&T Project (2012225016). The author Yicheng Ni is currently a Bayer Lecture Chair holder.

Conflict of interest

Xiaojun Qi, Haibo Shao, Jian Zhang, Ziping Sun, Yicheng Ni, Ke Xu declare that they have no financial relationships or conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yicheng Ni or Ke Xu.

Additional information

X. Qi and H. Shao contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qi, X., Shao, H., Zhang, J. et al. Radiopharmaceutical study on Iodine-131-labelled hypericin in a canine model of hepatic RFA-induced coagulative necrosis. Radiol med 120, 213–221 (2015). https://doi.org/10.1007/s11547-014-0433-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11547-014-0433-9

Keywords

Navigation