Evaluation of immunoconjugates of non-radioactive lutetium- and yttrium-rituximab – a vibrational spectroscopy study

Darinka Gjorgieva Ackova, Katarina Smilkov, Emilija Janevik-Ivanovska, Trajče Stafilov, Zorica Arsova-Sarafinovska, Petre Makreski

Abstract


Fourier Transform Infrared (FT-IR) and Raman spectroscopy were used to study the molecular structure of the recombinant monoclonal antibody and anti-CD20-conjugates which are intended to be used as anti-cancer therapeutic agents. We characterized the secondary structure of a therapeutic immunoconjugates, formulated with different bifunctional chelating agents and labeled with non-radioactive lutetium and yttrium. The secondary structure content of all three immunoconjugates was assessed to be similar to that of unlabeled antibody. In addition, no significant changes upon lyophilizing procedures were observed. The results demonstrate that amide bands could be taken as analytical peak which enables quick and reliable way for screening of protein pharmaceuticals during development of lyophilized formulations.


Keywords


Rituximab; bifunctional chelating agents; Infrared; Raman Spectroscopy

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A. Hagenbeek, V. Lewington, Report of a European Consensus 1. Workshop to develop recommendations for the optimal use of 90Y-Ibritumomab tiuxetan (Zevalin) in lymphoma, Ann. Oncol., 16, 786-792 (2005).

R.O. Dillman, Monoclonal antibody therapy for lymphoma, Cancer Pract., 9, 71–80 (2001).

R.O. Dillman, Magic bullets at last! Finally – approval of a monoclonal antibody for the treatment of cancer!!! Cancer Biother. Radiopharm., 12, 223–225 (1997).

R.O. Dillman, Treatment of low-grade B-cell lymphoma with the monoclonal antibody rituximab, Semin. Oncol., 30, 434–447 (2003).

R.O. Dillman, Radiolabeled anti-CD20 monoclonal antibodies for the treatment of B-cell lymphoma, J. Clin. Oncol., 20, 3545–3557 (2002).

B.D. Cheson, Radioimmunotherapy of non-Hodgkin’s lymphoma, Blood, 101, 391–398 (2003).

C.R. Dias, S. Jeger, J.A. Jr. Osso, C. Müller, C. De Pasquale, A. Hohn, R. Waibel, R. Schibli, Radiolabeling of rituximab with 188Re and 99mTc using the tricarbonyl technology, Nucl. Med. Biol., 38, 19-28 (2011).

S. Liu, Bifunctional coupling agents for radiolabeling of biomolecules and target-specific delivery of metallic radionuclides, Adv. Drug Deliver. Rev., 60, 1347-1370 (2008).

S. Liu, The role of coordination chemistry in the development of target-specific radiopharmaceuticals, Chem. Soc. Rev., 33, 445-461 (2004).

P. Thakral, S. Singla, M.P. Yadav, A. Vasisht, A. Sharma, S.K. Gupta, C.S. Bal, A. Malhotra, An approach for conjugation of 177Lu-DOTA-SCN-Rituximab (BioSim) & its evaluation for radioimmunotherapy of relapsed & refractory B-cell non Hodgkins lymphoma patients, Indian J. Med. Res., 139, 544-554 (2014).

H. Mohsin, J. Fitzsimmons, T. Shelton, T.J. Hoffman, C.S. Cutler, M.R. Lewis, P.S. Athey, G. Gulyas, G.E. Kiefer, R.K. Frank, J. Simon, S.Z. Lever, S.S. Jurisson, Preparation and biological evaluation of 111In, 177Lu and 90Y labeled DOTA analogues conjugated to B72.3, Nucl. Med. Biol., 34, 493–502 (2007).

A.T. Yordanov, M. Hens, C. Pegram, D.D. Bigner, M.R. Zalutsky, Antitenascin antibody 81C6 armed with 177Lu: in vivo comparison of macrocyclic and acyclic ligands, Nucl. Med. Biol., 34, 173–183 (2007).

S. Rasaneh, H. Rajabi, M.H. Babaei, F.J. Daha, Toxicity of trastuzumab labeled 177Lu on MCF7 and SKBr3 cell lines, Appl. Radiat. Isot., 68, 1964-1966 (2010).

M. Hens, G. Vaidyanathan, P. Welsh, M.R. Zalutsky, Labeling internalizing anti-epidermal growth factor receptor variant III monoclonal antibody with 177Lu: in vitro comparison of acyclic and macrocyclic ligands, Nucl. Med. Biol., 36, 117–128 (2009).

J. Hoffend, W. Mier, J. Schuhmacher, K. Schmidt, A. Dimitrakopoulou-Strauss, L.G. Strauss, E.R.M. Kinscherf, U. Haberkorna, Gallium-68-DOTA-albumin as a PET blood-pool marker: experimental evaluation in vivo, Nucl. Med. Biol., 32, 287–292 (2005).

M.R. McDevitt, D. Ma, J. Simon, K. Frank, D.A. Scheinberg, Design and synthesis of 225Ac radioimmunopharmaceuticals, Appl. Radiat. Isot., 57, 841–847 (2002).

C.J. Smith, H. Galib, G.L. Sieckmanc, D.L. Hayes, N.K. Owen, D.J. Mazuru, W.A. Volkert, T.J. Hoffman, Gastrin releasing peptide (GRP) receptor targeted radiopharmaceuticals: a concise update, Nucl. Med. Biol., 30, 101–109 (2003).

L.L. Chappell, E. Dadachova, D.E. Milenic, K. Garmestani, C. Wu, M.W. Brechbiel, Synthesis, characterization, and evaluation of a novel bifunctional chelating agent for the lead isotopes 203Pb and 212Pb, Nucl. Med. Biol., 27, 93–100 (2000).

J.L. Cleland, M.F. Powell, S.J. Shire, Development of stabile protein formulations: A close look at protein aggregation, deamidation, and oxidation, Crit. Rev. Ther. Drug Carrier Syst., 10, 307-377 (1993).

M. Paul, V. Vieillard, E. Jaccoulet, A. Astier, Long-term stability of diluted solutions of the monoclonal antibody rituximab, Int. J. Pharm., 436, 282– 290 (2012).

A. Bhambhani, J.T. Blue, Lyophilization strategies for development of a high-concentration monoclonal antibody formulation: benefits and pitfalls, Am. Pharm. Rev., 13, 31–38 (2010).

J. Park, K. Nagapudi, C. Vergara, R. Ramachander, J.S. Laurence, S. Krishnan, Effect of pH and Excipients on Structure, Dynamics, and Long-Term Stability of a Model IgG1 Monoclonal Antibody upon Freeze-Drying, Pharm. Res., 30, 968-984 (2013).

M. Rankl, T. Ruckstuhl, M. Rabe, G.R.J. Artus, A. Walser, S. Seeger, Conformational reorientation of immunoglobulin G during nonspecific interaction with surfaces, Chem. Phys. Chem., 7, 837–846 (2006).

B.M. Murphy, N. Zhang, R.W. Payne, J.M. Davis, A.M. Abdul-Fattah, J.E. Matsuura, A.C. Herman, M.C. Manning, Structure, stability, and mobility of a lyophilized IgG1 monoclonal antibody as determined using second-derivative infrared spectroscopy, J. Pharm. Sci., 101, 81-91 (2012).

D.M. Bunk, M.J. Welch, Electrospray ionization mass spectrometry for the quantitation of albumin in human serum, J. Am. Soc. Mass Spectr., 8, 1247-1254 (1997).

Z-Q. Wen, Raman Spectroscopy of protein pharmaceuticals, J. Pharm. Sci., 96, 2861-2878 (2007).

S. Krimm, J. Bandekar, Vibrational spectroscopy and conformation of peptides, polypeptides, and proteins, Adv. Protein. Chem., 38, 181–364 (1986).

R.W. William, Protein secondary structure analysis using Raman Amide I and Amide III spectra, Method Enzymol., 130, 311–331 (1986).

J. Banker, Amide modes and protein conformation, Biochim. Biophys. Acta, 1120, 123−143 (1992).

J. Kong, S. Yu, Fourier Transform Infrared Spectroscopic Analysis of Protein Secondary Structures, Acta Biochim. Biophys. Sin., 39, 549-559 (2007).

J.T. Pelton, L.R. McLean, Spectroscopic methods for analysis of protein secondary structure, Anal. Biochem., 277, 167–176 (2000).

A. Dong, T.W. Randolph, J.F. Carpenter, Entrapping intermediates of thermal aggregation in α-helical proteins with low concentration of guanidine hydrochloride, J. Biol. Chem., 275, 27689−27693 (2000).

R.P. Kengne-Momo, P. Daniel, F. Lagarde, Y.L. Jeyachandran, J.F. Pilard, M.J. Durand-Thouand, G. Thouand, Protein Interactions Investigated by the Raman Spectroscopy for Biosensor Applications, Int. J. Spectrosc., 2012, Article ID 462901, 7 pages (2012).

A. Rygula, K. Majzner, K.M. Marzec, A. Kaczor, M. Pilarczyka, M. Baranska, Raman spectroscopy of proteins: a review, J. Raman Spectrosc., 44, 1061–1076 (2013).

S. Nitahara, M. Maeki, H. Yamaguchi, K. Yamashita, M. Miyazaki, H. Maeda, Three-dimensional Raman spectroscopic imaging of protein crystals deposited on a nanodroplet, Analyst, 137, 5730-5735 (2012).

M. Marquart, J. Deisenhofer, R. Huber, Crystallographic refinement and atomic models of the intact immunoglobulin molecule Kol and its antigen-binding fragment at 3.0 θ and 1.9θ resolution, J. Mol. Biol., 141, 369–391 (1980).

H. Schulz, M. Baranska, Identification and quantification of valuable plant substances by IR and Raman spectroscopy, Vib. Spectr., 43, 13-25 (2007).

G. Reiter, N. Hassler, V. Weber, D. Falkenhagen, U.P. Fringeli, In situ FTIR ATR spectroscopic study of the interaction of immobilized human tumor necrosis factor-a with a monoclonal antibody in aqueous environment, Biochim. Biophys. Acta, 1699, 253-261 (2004).

S.U. Sane, R. Wong, C.C. Hsu, Raman spectroscopic characterization of drying-induced structural changes in a therapeutic antibody: Correlating structural changes with long-term stability, J. Pharm. Sci., 93, 1005–1018, 2004.

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

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




DOI: http://dx.doi.org/10.20450/mjcce.2015.627

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