Skip to main content
SpringerLink
Log in

Biological evaluation of [99mTc]Tc-labeled Buthus martensii Karsch Chlorotoxin peptide for glioma imaging

  • Published:
Journal of Radioanalytical and Nuclear Chemistry Aims and scope Submit manuscript

Abstract

This study was to investigate the synthesis and biological evaluation of [99mTc]Tc-labeled Buthus martensii Karsch Chlorotoxin ([99mTc]Tc-BmK CT) as a radiopharmaceutical for glioma single photon computed emission tomography (SPECT) imaging. The results showed that BmK CT peptide modified with a hexahistidine tag displayed good cytocompatibility in vitro, and could be efficiently radiolabeled with 99mTc via [99mTc]Tc-tricarbonyl chemistry. The [99mTc]Tc-BmK CT showed satisfactory radiochemical purity and stability in vitro, and could be developed as a probe for targeted SPECT imaging of glioma cells in vitro and in a tumor-bearing mouse model. Our data indicated that the synthesized [99mTc]Tc-BmK CT might be developed as a promising imaging agent for glioma diagnostic application.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Lim M, Xia Y, Bettegowda C, Weller M (2018) Current state of immunotherapy for glioblastoma. Nat Rev Clin Oncol 15(7):422–442

    Article  CAS  PubMed  Google Scholar 

  2. Bush NAO, Chang SM, Berger MS (2017) Current and future strategies for treatment of glioma. Neurosurg Rev 40(1):1–14

    Article  PubMed  Google Scholar 

  3. Chen R, Cohen AL, Colman H (2016) Targeted therapeutics in patients with high-grade gliomas: past, present, and future. Curr Treat Options Oncol 17(8):42

    Article  PubMed  Google Scholar 

  4. Weller M, Wick W, Aldape K, Brada M, Berger M, Pfister SM, Nishikawa R, Rosenthal M, Wen PY, Stupp R, Reifenberger G (2015) Glioma. Nat Rev Dis Primers 1(1):15017

    Article  PubMed  Google Scholar 

  5. Cohen G, Burks SR, Frank JA (2018) Chlorotoxin—a multimodal imaging platform for targeting glioma tumors. Toxins 10(12):496

    Article  CAS  PubMed Central  Google Scholar 

  6. Parrish-Novak J, Byrnes-Blake K, Lalayeva N, Burleson S, Fidel J, Gilmore R, Gayheart-Walsten P, Bricker GA, Crumb WJ, Tarlo KS, Hansen S, Wiss V, Malta E, Dernell WS, Olson JM, Miller DM (2017) Nonclinical profile of BLZ-100, a tumor-targeting fluorescent imaging agent. Int J Toxicol 36(2):104–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Qiao W, Zhao L, Wu S, Liu C, Guo L, Xing Y, Zhao J (2017) SPECT imaging and radionuclide therapy of glioma using 131I labeled Buthus martensii Karsch chlorotoxin. J Neurooncol 133(2):287–295

    Article  CAS  PubMed  Google Scholar 

  8. Hockaday DC, Shen S, Fiveash J, Raubitschek A, Colcher D, Liu A, Alvarez V, Mamelak AN (2005) Imaging glioma extent with 131I-TM-601. J Nucl Med 46(4):580–586

    CAS  PubMed  Google Scholar 

  9. Mamelak AN, Rosenfeld S, Bucholz R, Raubitschek A, Nabors LB, Fiveash JB, Shen S, Khazaeli MB, Colcher D, Liu A, Osman M, Guthrie B, Schade-Bijur S, Hablitz DM, Alvarez VL, Gonda MA (2006) Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma. J Clin Oncol 24(22):3644–3650

    Article  CAS  PubMed  Google Scholar 

  10. Shen S, Khazaeli MB, Gillespie G, Alvarez VL (2003) Radiation dosimetry of I-131-TM-601 peptide for synergistic targeted radiotherapy for malignant glioma in mice. J Neurooncol 71(2):113–119

    Article  Google Scholar 

  11. Fu Y, An N, Chan K, Wu Y, Zheng S, Liang A (2011) A model of BmK CT in inhibiting glioma cell migration via matrix metalloproteinase-2 from experimental and molecular dynamics simulation study. Biotechnol Lett 33(7):1309–1317

    Article  CAS  PubMed  Google Scholar 

  12. Lin X, Ruan Q, Lin L, Zhang X, Duan X, Teng Y, Zhang J (2018) Biological evaluation and SPECT imaging of tumor hypoxia using a novel technetium-99m labeled tracer with 2-nitroimidazole moiety. J Radioanal Nucl Chem 317(3):1463–1468

    Article  CAS  Google Scholar 

  13. De Saint-Hubert M, Mottaghy FM, Vunckx K, Nuyts J, Fonge H, Prinsen K, Stroobants S, Mortelmans L, Deckers N, Hofstra L, Reutelingsperger CPM, Verbruggen A, Rattat D (2010) Site-specific labeling of ‘second generation’ annexin V with 99mTc(CO)3 for improved imaging of apoptosis in vivo. Bioorg Med Chem 18(3):1356–1363

    Article  PubMed  Google Scholar 

  14. Carpenet H, Cuvillier A, Monteil J, Quelven I (2015) Anti-CD20 immunoglobulin G radiolabeling with a 99mTc-tricarbonyl core: in vitro and in vivo evaluations. PLoS ONE 10(10):e0139835

    Article  PubMed  PubMed Central  Google Scholar 

  15. Zhang X, Teixeira V, Porcal W, Cabral P, Gambini J-P, Fernandez M, Gallazzi F, Quinn P T (2014) [99mTc(CO)3]+ and [99mTcO2]+ Radiolabeled cyclic melanotropin peptides for melanoma SPECT imaging. Curr Radiopharm 7(1):63–74

    Article  CAS  PubMed  Google Scholar 

  16. Xing Y, Chand G, Liu C, Cook GJR, O’Doherty J, Zhao L, Wong NCL, Meszaros LK, Ting HH, Zhao J (2019) Early phase I study of a 99mTc-labeled anti-programmed death ligand-1 (PD-L1) single-domain antibody in SPECT/CT assessment of PD-L1 expression in non-small cell lung cancer. J Nucl Med 60(9):1213–1220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wu S, Ma K, Qiao W, Zhao L, Liu C, Guo L, Xing Y, Zhu M, Zhao J (2018) Anti-metastatic effect of 131I-labeled Buthus martensii Karsch chlorotoxin in gliomas. Int J Mol Med 42(6):3386–3394

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Du J, Fu Y, Wang J, Liang A (2013) Adenovirus-mediated expression of BmK CT suppresses growth and invasion of rat C6 glioma cells. Biotechnol Lett 35(6):861–870

    Article  CAS  PubMed  Google Scholar 

  19. Sun N, Zhao L, Qiao W, Xing Y, Zhao J (2017) BmK CT and 125I-BmK CT suppress the invasion of glioma cells in vitro via matrix metalloproteinase-2. Mol Med Rep 15(5):2703–2708

    Article  CAS  PubMed  Google Scholar 

  20. Banks WA (2016) From blood–brain barrier to blood–brain interface: new opportunities for CNS drug delivery. Nat Rev Drug Discov 15(4):275–292

    Article  CAS  PubMed  Google Scholar 

  21. Veiseh O, Gunn JW, Kievit FM, Sun C, Fang C, Lee JS, Zhang M (2009) Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles. Small 5(2):256–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The work was financially supported by the National Natural Science Foundation of China (81671712 and 81801727), and the Ningxia Key Research and Development Program (2019BEG03018).

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080, People’s Republic of China

    Changcun Liu, Tiantian Wang & Jinhua Zhao

  2. Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, People’s Republic of China

    Changcun Liu, Lingzhou Zhao, Wenli Qiao & Jinhua Zhao

  3. School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, Ningxia, People’s Republic of China

    Meilin Zhu

  4. Department of Nuclear Medicine, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, People’s Republic of China

    Jiqin Yang

Authors
  1. Changcun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiantian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lingzhou Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenli Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Meilin Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiqin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jinhua Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Meilin Zhu, Jiqin Yang or Jinhua Zhao.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, C., Wang, T., Zhao, L. et al. Biological evaluation of [99mTc]Tc-labeled Buthus martensii Karsch Chlorotoxin peptide for glioma imaging. J Radioanal Nucl Chem 326, 193–199 (2020). https://doi.org/10.1007/s10967-020-07293-4

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10967-020-07293-4

Keywords

Search

Navigation