Skip to main content
Log in

Vibrational spectroscopy as a tool for examination to the secondary structure of metal-labeled trastuzumab immunoconjugates

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

Abstract

Infrared and Raman spectroscopy are effective techniques that allow collecting information about secondary structure of proteins, including antibodies. Trastuzumab, antibody used in our study was in a freeze-dried form, conjugated with different bifunctional chelators and linked with the stable isotopes of lutetium and yttrium. The characterization of the final immunoconjugates showed no significant changes in the structure demonstrated by the presence of the amide bands characteristic for a α-helices and β-sheets structures. These methods could be applied during the production of the antibody freeze-dried kit formulations for the labeling with the radioactive isotopes.

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

Similar content being viewed by others

References

  1. Mehren M, Adams GA, Weiner LM (2003) Monoclonal antibody therapy for cancer. Annu Rev Med 54:343–369

    Article  CAS  Google Scholar 

  2. Baselga J (2001) Clinical trials of herceptin (trastuzumab). Eur J Cancer 37(1):S18–S24

    Article  CAS  PubMed  Google Scholar 

  3. Sharkey RM, Goldenberg DM (2006) Targeted therapy of cancer: new prospects for antibodies and immunoconjugates. CA Cancer J Clin 56(4):226–243

    Article  PubMed  Google Scholar 

  4. Pastan I, Hassan R, FitzGerald DJ, Kreitman RJ (2006) Immunotoxin therapy of cancer. Cancer 6(7):559–565

    CAS  PubMed  Google Scholar 

  5. Boswell CA, Brechbiel MW (2007) Development of radioommunotherapeutic and diagnostic antibodies: an inside-out view. Nucl Med Biol 34(7):757–778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Leonard JP (2005) Targeting CD20 in follicular NHL: novel anti-CD20 therapies, antibody engineering, and the use of radioimmunoconjugates. Hematology. 2005(1):335–339

    Article  Google Scholar 

  7. Hooge MNL, Kosterink JGW, Perik PJ, Nijnuis H, Tran L, Bart J, Suurmeijer AJH, de Jong S, Jager PL, de Vries EGE (2004) Preclinical characterization of 111In-DTPA-trastuzumab. Br J Pharmacol 143(1):99–106

    Article  CAS  Google Scholar 

  8. Perik PJ, Hooge MNL, Gietema JA, Graaf WTA, Korte MA, Jonkman S, Kosterink JGW, Veldhuisen VJ, Sleijfer DT, Jager PL, Vries EGE (2006) Indium-111–labeled trastuzumab scintigraphy in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer. J Clin Oncol 24(15):2276–2282

    Article  CAS  PubMed  Google Scholar 

  9. McLarty K, DA CornelissenB Scollard, Done SJ, Chun K, Reilly (2009) RM Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumor xenografts. Eur J Nucl Med Mol Imaging 36(1):81–93

    Article  CAS  PubMed  Google Scholar 

  10. Alirezapour B, Jalilian AR, Bolourinovin F, Moradkhani DS (2013) Production and quality control of [67Ga]-DOTA-trastuzumab for radioimmunoscintigraphy. Iran J Pharm Res 12(2):355–366

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Palm S, Enmon RM, Matei C, KolbertK XuS, Zanzonico PB, Finn RL, Koutcher JA, Larson SM, Sgouros G (2003) Pharmacokinetics and biodistribution of 86Y-trastuzumab for 90Y dosimetry in an ovarian carcinoma model: correlative microPET and MRI. J Nucl Med 44(7):1148–1155

    CAS  PubMed  Google Scholar 

  12. Rasaneh S, Rajabi H, Akhlaghpoor S, Sheybani S (2012) Radioimmunotherapy of mice bearing breast tumor with 177Lu-labeled trastuzumab. Turk J Med Sci 42(1):1292–1298

    CAS  Google Scholar 

  13. Heyerdahl H, Abbas N, Brevik EM, Mollatt C, Dahle J (2012) Fractionated therapy of HER2-expressing breast and ovarian cancer xenografts in mice with targeted alpha emitting 227Th-DOTA-p-benzyl-trastuzumab. PLoS ONE 7(8):1–14

    Article  CAS  Google Scholar 

  14. Brechbiel MW (2008) Bifunctional chelates for metal nuclides. Q J Nucl Med Mol Imaging 52(2):166–173

    CAS  PubMed  Google Scholar 

  15. Shire SJ (2009) Formulation and manufacturability of biologics. Curr Opin Biotechnol 20(6):1–7

    Article  CAS  Google Scholar 

  16. Kong J, Shaoning YU (2007) Fourier transform infrared spectroscopic analysis of the protein secondary structure. Acta Biochim Biophys Sin 39(8):549–559

    Article  CAS  PubMed  Google Scholar 

  17. Tuma R (2005) Raman spectroscopy of proteins: from peptides to large assemblies. J Raman Spectrosc 36(4):307–319

    Article  CAS  Google Scholar 

  18. Barth A (2007) Infrared spectroscopy of proteins. Biochim Biophys Acta 1767(9):1073–1101

    Article  CAS  PubMed  Google Scholar 

  19. Krimm S (1983) Vibrational analysis of conformation in peptides, polypeptides and proteins. Biopolymers 22:217–225

    Article  CAS  PubMed  Google Scholar 

  20. Woutersen S, Hamm P (2002) Nonlinear two-dimensional vibrational spectroscopy of peptides. J Phys Condens Matter 14(39):R1035–R1062

    Article  CAS  Google Scholar 

  21. Kengne-Momo RP, Daniel P, Lagarde F, Jeyachandran YL, Pilard JF, Durand-Thouand MJ, Thouand G (2012) Protein interactions investigated by the Raman spectroscopy for biosensor applications. Int J Spectrosc 2012:1–7

    Article  CAS  Google Scholar 

  22. Fabian H, Mantele W (2002) Infrared spectroscopy of proteins. Biochem Appl 5:3426–3452

    Google Scholar 

  23. Nesvizhskii AI, Keller A, Kolker E, Aebersold R (2003) A statistical model for identifying proteins by tandem mass spectrometry. Anal Chem 75(17):4646–4658

    Article  CAS  PubMed  Google Scholar 

  24. Greenfield NJ (2006) Using circular dichroism spectra to estimate protein secondary structure. Nat Protoc 1(6):1876–2890

    Google Scholar 

  25. Mielke SP, Krishnan VV (2009) Characterization of protein secondary structure from NMR chemical shifts. Prog Nucl Magn Reson Spectrosc 54(3–4):141–165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Smyth MS, Martin JHJ (2000) X-ray crystallography. J Clin Pathol Mol Pathol 53(1):8–14

    Article  CAS  Google Scholar 

  27. Gjorgieva Ackova D, Smilkov K, Janevik-Ivanovska E (2014) Formulation and characterization of “Ready to Use” 1B4M-DTPA-rituximab for Lu-177 labeling. World J Med Sci 11(4):535–540

    Google Scholar 

  28. Vermeer AWP, Norde W (2000) The thermal stability of immunoglobulin: unfolding and aggregation of a multi-domain protein. Biophys J 78(1):394–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Degardin K, Desponds A, Roggo Y (2017) Protein-based medicines analysis by Raman spectroscopy for the detection of counterfeits. Forensic Sci Int 278:313–325

    Article  CAS  PubMed  Google Scholar 

  30. Harris LJ, Skaletsky E, McPherson A (1998) Crystallographic structure of an intact IgG1 monoclonal antibody. J Mol Biol 275(5):861–872

    Article  CAS  PubMed  Google Scholar 

  31. Wen ZQ (2007) Raman spectroscopy of protein pharmaceuticals. J Pharm Sci 96(11):2861–2878

    Article  CAS  PubMed  Google Scholar 

  32. Baker AE, Mantz AR, Chiu ML (2014) Raman spectroscopy characterization of antibody phases in serum. MAbs 6(6):1509–1517

    Article  PubMed  PubMed Central  Google Scholar 

  33. Paudel R, Raijada D, Rantanen J (2015) Raman spectroscopy in pharmaceutical product design. Adv Drug Deliv Rev 89:3–20

    Article  CAS  PubMed  Google Scholar 

  34. Fu F, DeOliveira DB, Trumble WR, Sarkar HK, Singh BR (1994) Secondary structure estimation of protein using the amide III refion of fourier transform infrared spectroscopy: application to analyze calcium-binding-induced structural changes in calsequestrin. Appl Spectrosc 48(11):1432–1441

    Article  CAS  Google Scholar 

  35. Wang Y, Boysen RI, Wood BR, Kansiz M, McNaughton D, Hearn MTW (2008) Determination of the secondary structure of proteins in different environments by FTIR-ATR spectroscopy and PLS regression. Biopolymers 89(11):895–905

    Article  CAS  PubMed  Google Scholar 

  36. Gjorgieva Ackova D, Smilkov K, Janevik-Ivanovska E, Stafilov T, Arsova-Sarafinovska Z, Makreski P (2015) Evaluation of non-radioactive lutetium- and yttrium-labeled immunoconjugates of rituximab—a vibrational spectroscopy study. Maced J Chem Eng 34(2):351–362

    Article  Google Scholar 

  37. Takeuchi H (2011) UV Raman markers for structural analysis of aromatic side chain in proteins. Anal Sci 27(11):1077–1086

    Article  CAS  PubMed  Google Scholar 

  38. Liu H, May K (2012) Disulfide bond structures of IgG molecules, structural variations, chemical modifications and possible impacts to stability and biological function. MAbs 4(1):17–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Cuesta RG, Goodacre R, Ashton L (2014) Monitoring antibody aggregation in early drug development using raman spectroscopy and perturbation-correlation moving windows. Anal Chem 86(22):11133–11140

    Article  CAS  Google Scholar 

  40. Schule S, Frieb W, Bechtold-Peters K, Garidel P (2007) Conformational analysis of protein secondary structure during spray-drying of antibody/mannitol formulations. Eur J Pharm Biopharm 65(1):1–9

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant No. 172044) and by the University Goce Delcev, Faculty of Medical Sciences, Stip, Republic of Macedonia (Grant No. 0201-165/6). Commercial Herceptin® was provided by University Clinic for Radiotherapy and Oncology, Skopje. The authors thank R&D Institute, Alkaloid AD, Skopje for making available the ATR-IR instrumentation to collect the corresponding spectra.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. Janevik-Ivanovska.

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

Sterjova, M., Džodić, P., Makreski, P. et al. Vibrational spectroscopy as a tool for examination to the secondary structure of metal-labeled trastuzumab immunoconjugates. J Radioanal Nucl Chem 320, 209–218 (2019). https://doi.org/10.1007/s10967-019-06450-8

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10967-019-06450-8

Keywords

Navigation