Nuclear Medicine and Biology
Volume 36, Issue 4 , Pages 395-402 , May 2009

A simplified suite of methods to evaluate chelator conjugation of antibodies: effects on hydrodynamic radius and biodistribution

  • Fares Al-Ejeh

      Affiliations

    • Experimental Therapeutics Laboratory, Hanson Institute, Adelaide SA 5000, Australia
  • ,
  • Jocelyn M. Darby

      Affiliations

    • Experimental Therapeutics Laboratory, Hanson Institute, Adelaide SA 5000, Australia
  • ,
  • Benjamin Thierry

      Affiliations

    • Ian Wark Research Institute, University of South Australia, Adelaide SA 5000, Australia
  • ,
  • Michael P. Brown

      Affiliations

    • Experimental Therapeutics Laboratory, Hanson Institute, Adelaide SA 5000, Australia
    • Department of Medical Oncology, Royal Adelaide Hospital Cancer Centre, and School of Medicine, University of Adelaide, Adelaide SA 5000, Australia
    • Corresponding Author InformationCorresponding author. Department of Medical Oncology, Royal Adelaide Hospital, MDP 11, Level 4, East Wing, North Terrace, Adelaide SA 5000, Australia. Tel.: +61 8 8222 4398; fax: +61 8 8222 4358.

Received 13 November 2008 ,Revised 18 December 2008 ,Accepted 13 January 2009.

References 

  1. Waldmann TA. Monoclonal antibodies in diagnosis and therapy. Science. 1991;252:1657–1662
  2. O'Donoghue JA, Bardies M, Wheldon TE. Relationships between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides. J Nucl Med. 1995;36:1902–1909
  3. Liu S, Edwards DS. Bifunctional chelators for therapeutic lanthanide radiopharmaceuticals. Bioconjug Chem. 2001;12:7–34
  4. Brady ED, Chong HS, Milenic DE, Brechbiel MW. Development of a spectroscopic assay for bifunctional ligand-protein conjugates based on copper. Nucl Med Biol. 2004;31:795–802
  5. Dadachova E, Chappell LL, Brechbiel MW. Spectrophotometric method for determination of bifunctional macrocyclic ligands in macrocyclic ligand-protein conjugates. Nucl Med Biol. 1999;26:977–982
  6. Pippin CG, McMurry TJ, Brechbiel MW, McDonald M, Lambrecht R, et al. Lead(II) complexes of 1,4,7,10-tetraazacyclododecane-N,N′,N″,N″-tetraacetate: solution chemistry and application to tumor localization with 203Pb labeled monoclonal antibodies. Inorg Chim Acta. 1995;239:43–51
  7. Pippin CG, Parker TA, McMurry TJ, Brechbiel MW. Spectrophotometric method for the determination of a bifunctional DTPA ligand in DTPA-monoclonal antibody conjugates. Bioconjug Chem. 1992;3:342–345
  8. Kukis DL, DeNardo GL, DeNardo SJ, Mirick GR, Miers LA, et al. Effect of the extent of chelate substitution on the immunoreactivity and biodistribution of 2IT-BAT-Lym-1 immunoconjugates. Cancer Res. 1995;55:878–884
  9. Al-Ejeh F, Darby JM, Brown MP. The La autoantigen is a malignancy-associated cell death target that is induced by DNA-damaging drugs. Clin Cancer Res. 2007;13:5509s–5518s
  10. Al-Ejeh F, Darby JM, Pensa K, Diener KR, Hayball JD, et al. In vivo targeting of dead tumor cells in a murine tumor model using a monoclonal antibody specific for the La autoantigen. Clin Cancer Res. 2007;13:5519s–5527s
  11. Wang TS, Ng AK, Alsedairy S, Fawwaz RA, Hardy MA, et al. A method for direct quantification of the amount of DTPA in 111In monoclonal antibody preparations. Int J Rad Appl Instrum [A]. 1987;38:315–319
  12. Brechbiel MW, Gansow OA, Atcher RW, Schlom J, Esteban J, et al. Synthesis of 1-(p-isothiocyanatobenzyl) derivatives of DTPA and EDTA. Antibody labeling and tumor-imaging studies. Inorg Chem. 1986;25:2772–2781
  13. Brandt KD, Schnobrich KE, Johnson DK. Characterization of antibody-chelator conjugates: determination of chelator content by terbium fluorescence titration. Bioconjug Chem. 1991;2:67–70
  14. Pham DT, Kaspersen FM, Bos ES. Electrophoretic method for the quantitative determination of a benzyl-DTPA ligand in DTPA monoclonal antibody conjugates. Bioconjug Chem. 1995;6:313–315
  15. Jaggi JS, Carrasquillo JA, Seshan SV, Zanzonico P, Henke E, et al. Improved tumor imaging and therapy via i.v. IgG-mediated time-sequential modulation of neonatal Fc receptor. J Clin Invest. 2007;117:2422–2430
  16. Knogler K, Grunberg J, Novak-Hofer I, Zimmermann K, Schubiger PA. Evaluation of 177Lu-DOTA-labeled aglycosylated monoclonal anti-L1-CAM antibody chCE7: influence of the number of chelators on the in vitro and in vivo properties. Nucl Med Biol. 2006;33:883–889
  17. Brouwers AH, van Eerd JE, Frielink C, Oosterwijk E, Oyen WJ, et al. Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re. J Nucl Med. 2004;45:327–337

PII: S0969-8051(09)00008-0

doi: 10.1016/j.nucmedbio.2009.01.001

Nuclear Medicine and Biology
Volume 36, Issue 4 , Pages 395-402 , May 2009