Cytotoxicity with Auger electron-emitting radionuclides delivered by antibodies

Gary L. Griffiths, Serengulam V. Govindan, George Sgouros, Gaik Lin Ong, David M. Goldenberg, M. Jules Mattes

Research output: Contribution to journalArticle

Abstract

We investigated the in vitro cytotoxic potential of Auger electron- emitting radionuclides delivered to the cytoplasm or, more specifically, to lysosomes, via antibodies. The antibody (Ab) used was LLI, which is specific for CD74, an epitope of the major histocompatibility complex (MHC) class II antigen invariant chain, Ii, present on the cell surface. It is taken up in large amounts, approximately 107 Ab molecules per cell per day, and delivered to lysosomes. The radioisotopes tested included 111In, 99mTc and 125I. With sufficient specific activity, approximately 10 mCi/mg Ab, all of these isotopes were potent cytotoxic agents, 125I was active only if a 'residualizing' form was used, meaning a form that is trapped within cells after catabolism of the Ab to which it was conjugated (conventional oxidative iodination produces a non-residualizing label). The conjugates of 111In and 99mTc used are known to be residualizing. One hundred percent cell kill in vitro was obtained with 111In and 125I, under conditions in which a non-reactive control Ab; conjugated in the same way, produced no significant toxicity. 99mTc was also potent and specific, but appeared somewhat less active than the other isotopes under the conditions evaluated. Although few Abs are accreted by cells at the same rate as LLI, it may be possible to use other Abs to deliver similar amounts of radioactivity, if Abs with higher specific activity can be produced. Such conjugated radioisotopes may be useful for attacking tumor cells in vivo, particularly for single cells or micrometastases.

Original languageEnglish (US)
Pages (from-to)985-992
Number of pages8
JournalInternational Journal of Cancer
Volume81
Issue number6
DOIs
StatePublished - 1999
Externally publishedYes

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Radioisotopes
Electrons
Antibodies
Lysosomes
Isotopes
Neoplasm Micrometastasis
Halogenation
Histocompatibility Antigens Class II
Cytotoxins
Major Histocompatibility Complex
Radioactivity
Epitopes
Cytoplasm
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cytotoxicity with Auger electron-emitting radionuclides delivered by antibodies. / Griffiths, Gary L.; Govindan, Serengulam V.; Sgouros, George; Ong, Gaik Lin; Goldenberg, David M.; Mattes, M. Jules.

In: International Journal of Cancer, Vol. 81, No. 6, 1999, p. 985-992.

Research output: Contribution to journalArticle

Griffiths, Gary L. ; Govindan, Serengulam V. ; Sgouros, George ; Ong, Gaik Lin ; Goldenberg, David M. ; Mattes, M. Jules. / Cytotoxicity with Auger electron-emitting radionuclides delivered by antibodies. In: International Journal of Cancer. 1999 ; Vol. 81, No. 6. pp. 985-992.
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