A comparative study of copper-67 radiolabeling and kinetic stabilities of antibody-macrocycle chelate conjugates

D. L. Kukis, H. Diril, D. P. Greiner, S. J. DeNardo, Gerald L Denardo, Q. A. Salako, C. F. Meares

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Background. The development of new chelating agents and radiolabeling protocols is essential to progress in radioimmunotherapy with antibody- chelate conjugates. Methods. Immunoconjugates of four polyazamacrocycles with N-bonded acetate groups were prepared by conjugation via 2-iminothiolane to Lym-1, a murine antilymphoma immunoglobulin G(2a) MoAb. To optimize 67Cu radiolabeling, complexation conditions were explored. The kinetic stabilities in vitro in human serum of four 67Cu labeled immunoconjugates were investigated. Results. Lym-1-2IT-6-BAT-67Cu, the chelate conjugate of 6- [p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N',N''N'''- tetraacetic acid, exhibited excellent kinetic stability in human serum, while Lym-1-2IT-2-BAT-67Cu, prepared from the structural isomer 2-[p- (bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''- tetraacetic acid, exhibited a markedly higher rate of loss of radiometal. It was observed that the radiolabeling ratio of Lym-1-2IT-6-BAT-67Cu, in mCi per mg immunoconjugate, was limited solely by the specific activity of the radiometal, which varied significantly from lot to lot. This ratio for a given lot of 67Cu can be predicted by a preliminary titration. Conclusions. The preparation of 67Cu labeled immunoconjugates of therapeutic quality has been improved by the determination of optimum radiolabeling conditions, and by development of a titration protocol which rapidly and accurately predicts the radiolabeling ratio in mCi per mg immunoconjugate. The surprising difference in the properties of 6-BAT and 2-BAT shows the exquisite dependence of kinetic stability on structure.

Original languageEnglish (US)
Pages (from-to)779-786
Number of pages8
Issue numberSUPPL.
StatePublished - 1994


  • antibody
  • chelates
  • copper-67
  • immunoconjugates
  • radioimmunotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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