Advertisement

Journal of Radioanalytical and Nuclear Chemistry

, Volume 322, Issue 2, pp 545–551 | Cite as

Indium-111 labeled bleomycin for targeting diagnosis and therapy of liver tumor: optimized preparation, biodistribution and SPECT imaging with xenograft models

  • Yu Tang
  • Weihao Liu
  • Feize Li
  • Lin Chen
  • Mingshuang WangEmail author
  • Yingjiang Hu
  • Zhonghui Liao
  • Yue Chen
  • Shufen Li
  • Jiali Liao
  • Jijun Yang
  • Yuanyou YangEmail author
  • Ning Liu
Article
  • 18 Downloads

Abstract

In this work, the preparation of 111In radiolabeled bleomycin (111In-BLM) was optimized systematically and used for SPECT imaging of liver cancer xenograft models. 111In-BLM with a high radiochemical yield (> 99%) could be obtained at pH 0.5–1 at a mixture ratio of 9:1 (111In/BLM, mCi/mg). The radiochemical purity of 111In-BLM retained > 99% in either buffers or serum for 3 days. Biodistribution of 111In-BLM revealed its excellent stability in vivo. The SPECT imaging studies showed 111In-BLM has great specificity to liver tumor xenograft. All the results implied 111In-BLM is a potential radiopharmaceutical for targeting diagnosis and therapy of liver tumor.

Keywords

111In-BLM 111In Liver cancer SPECT imaging 

Notes

Acknowledgements

This Study was supported by Key Research Development Project of Sichuan Provincial Department of Science and Technology (2018SZ0022), Strategic Cooperation Project of Luzhou Municipal People’s Government of Sichuan University (2018CDLZ-09) and the Open Project Program of Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province. We would like to thank the cyclotron operation crew Xiaodong Liao of Sichuan University for his help in performing irradiations. Besides, the authors thank Guangfu Liu and Chi Qi from the Affiliated Hospital of Southwest Medical University for their expert knowledge and technical advice for SPECT imaging.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Haeusler D et al (2018) Molecular Imaging: in vivo agents for the diagnosis and treatment of cancer. Contrast Media Mol Imaging 2018:1–2CrossRefGoogle Scholar
  2. 2.
    Gnanasegaran G, Ballinger JR (2014) Molecular imaging agents for SPECT (and SPECT/CT). Eur J Nucl Med Mol Imaging 41:S26–S35CrossRefGoogle Scholar
  3. 3.
    Brom M et al (2012) Improved labelling of DTPA- and DOTA-conjugated peptides and antibodies with 111In in HEPES and MES buffer. EJNMMI Res 2:4CrossRefGoogle Scholar
  4. 4.
    Rosenkranz AA et al (2018) Antitumor activity of auger electron emitter 111In delivered by modular nanotransporter for treatment of bladder cancer with EGFR overexpression. Front Pharmacol 9:1331CrossRefGoogle Scholar
  5. 5.
    Iikuni S et al (2018) Cancer radiotheranostics targeting carbonic anhydrase-IX with 111In- and 90Y-labeled ureidosulfonamide scaffold for SPECT imaging and radionuclide-based therapy. Theranostics 8:2992–3006CrossRefGoogle Scholar
  6. 6.
    Aghevlian S et al (2018) Panitumumab modified with metal-chelating polymers (MCP) complexed to 111In and 177Lu-An EGFR-targeted theranostic for pancreatic cancer. Mol Pharm 15:1150–1159CrossRefGoogle Scholar
  7. 7.
    Yarmohammadi M, Mirzaii M, Sadeghi M (2012) Chemical separation of enriched cadmium target from copper backing in cyclotron production of radioisotope 111In. J Radioanal Nucl Chem 295:987–990CrossRefGoogle Scholar
  8. 8.
    Esquinas PL et al (2018) Dual SPECT imaging of 111In and 67Ga to simultaneously determine in vivo the pharmacokinetics of different radiopharmaceuticals: a quantitative tool in pre-clinical research. Phys Med Biol 63:235029CrossRefGoogle Scholar
  9. 9.
    Ngo Ndjock Mbong G et al (2015) Trastuzumab labeled to high specific activity with 111In by site-specific conjugation to a metal-chelating polymer exhibits amplified auger electron-mediated cytotoxicity on HER2-positive breast cancer cells. Mol Pharm 12:1951–1960CrossRefGoogle Scholar
  10. 10.
    Chow TH et al (2009) Improvement of biodistribution and therapeutic index via increase of polyethylene glycol on drug-carrying liposomes in an HT-29 luc xenografted mouse model. Anticancer Res 29:2111–2120PubMedGoogle Scholar
  11. 11.
    Yua ZQ et al (2016) Targeted delivery of bleomycin a comprehensive anticancer review. Curr Cancer Drug Targets 16:509–521CrossRefGoogle Scholar
  12. 12.
    Chen J, Stubbe J (2005) Bleomycins: towards better therapeutics. Nat Rev Cancer 5:102–104CrossRefGoogle Scholar
  13. 13.
    Liu XS, Wang X (2011) Systematic curation of miRBase annotation using integrated small RNA high-throughput sequencing data for C. elegans and Drosophila. Front Genet 2:1–14CrossRefGoogle Scholar
  14. 14.
    Levi et al (1993) The importance of bleomycin in combination chemotherapy for good-prognosis germ-cell carcinoma. J Clin Oncol 11:1300–1305CrossRefGoogle Scholar
  15. 15.
    Hou DY et al (1983) Stability of bleomycin-111In in vivo properties compared with 57Co-bleomycin. Eur J Nucl Med 8:535–540CrossRefGoogle Scholar
  16. 16.
    Hou DY et al (1984) Distribution and stability of [111In] bleomycinand its fractions in tumor-bearing mice. Int J Nucl Med Biol 11:129–139CrossRefGoogle Scholar
  17. 17.
    Hou DY et al (1992) Distribution of 111I-bleomycin complex in small cell lung cancer cells by autoradiography. J Surg Oncol 49:93–97CrossRefGoogle Scholar
  18. 18.
    Horn NL et al (1975) Indium-111 bleomycin scanning in the evaluation of malignant melanoma. J Nucl Med 16:537Google Scholar
  19. 19.
    Soimakallio S, Kiuru A (1980) 111In-bleomycin imaging of breast tumors. Eur J Nucl Med 5:363–371CrossRefGoogle Scholar
  20. 20.
    Hou DY et al (1984) A new 111In-bleomycin complex for tumor imaging: preparation, stability, and distribution in glioma-bearing mice. J Surg Oncol 25:168–175CrossRefGoogle Scholar
  21. 21.
    Kairemo KJA et al (1994) A low pH In-111-bleomycin complex (BLM), a tracer for radiochemotherapy of head and neck cancer. J Nucl Biol Med 38:135–139PubMedGoogle Scholar
  22. 22.
    EngstromPE et al (1998) Salford dynamic gamma camera studies of 111In–bleomycin complex in normal and glioma bearing rats after in vivo electropermeabilization using exponential high-voltage pulses. Bioelectrochem Bioenerg 46:241–248CrossRefGoogle Scholar
  23. 23.
    Kalevi JA et al (1996) Indium-111 bleomycin complex for radiomotherapy of head and neck cancer- dosimetric and biokinetic aspects. Eur J Nucl Med 23:631–638CrossRefGoogle Scholar
  24. 24.
    Tsai WC et al (2018) Influence of the time interval from diagnosis to treatment on survival for early-stage liver cancer. PLoS ONE 13:19–32Google Scholar
  25. 25.
    Yang X et al (2014) Imaging of hepatocellular carcinoma patient-derived xenografts using 89Zr-labeled anti-glypican-3 monoclonal antibody. Biomater 35:6964–6971CrossRefGoogle Scholar
  26. 26.
    Hou DY et al (1984) Distribution and stability of [111In] bleomycinand its fractions in tumor-bearing mice. Int J Nucl Med Biol 11:129–139CrossRefGoogle Scholar
  27. 27.
    Tang Y et al (2019) A radiopharmaceutical [89Zr]Zr-DFO-nimotuzumab for immunoPET withepidermal growth factor receptor expression invivo. Nucl Med Biol 70:23–31CrossRefGoogle Scholar
  28. 28.
    Liu W et al (2018) One-step labelling of a novel small-molecule peptide with astatine-211: preliminary evaluation in vitro and in vivo. J Radioanal Nucl Chem 316:451–456CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2019

Authors and Affiliations

  1. 1.Key Laboratory of Radiation Physics and Technology (Sichuan University), Ministry of Education, Institute of Nuclear Science and TechnologySichuan UniversityChengduPeople’s Republic of China
  2. 2.Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University & Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan ProvinceSouthwest Medical UniversityLuzhouPeople’s Republic of China
  3. 3.Guo Ke Rong’ an Biological Technology (Beijing) Co. Ltd.BeijingPeople’s Republic of China

Personalised recommendations