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Cytotoxicity with Auger electron‐emitting radionuclides delivered by antibodies
Author(s) -
Griffiths Gary L.,
Govindan Serengulam V.,
Sgouros George,
Ong Gaik Lin,
Goldenberg David M.,
Mattes M. Jules
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990611)81:6<985::aid-ijc23>3.0.co;2-w
Subject(s) - cytotoxic t cell , in vivo , chemistry , antibody , epitope , radioimmunotherapy , major histocompatibility complex , in vitro , antigen , mhc class i , biochemistry , biology , microbiology and biotechnology , immunology , monoclonal antibody , genetics
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 LL1, 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 10 7 Ab molecules per cell per day, and delivered to lysosomes. The radioisotopes tested included 111 In, 99m Tc and 125 I. With sufficient specific activity, approximately 10 mCi/mg Ab, all of these isotopes were potent cytotoxic agents. 125 I 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 111 In and 99m Tc used are known to be residualizing. One hundred percent cell kill in vitro was obtained with 111 In and 125 I, under conditions in which a non‐reactive control Ab, conjugated in the same way, produced no significant toxicity. 99m Tc 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 LL1, 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. Int. J. Cancer 81:985–992, 1999. © 1999 Wiley‐Liss, Inc.