Pretargeting: General principles; October 10-12, 1996

David A. Goodwin, Claude F. Meares

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

BACKGROUND. Human imaging studies show that maximum human tumor concentrations of monoclonal antibody (MoAb) are achieved in 1 day, but several days are required for background reduction and sensitive radioimmunoscintigraphy of tumors. With therapeutic radionuclides such as ytrrium-90 (90Y), this long biologic half-life imposes a high radiation burden on sensitive normal tissues from the large amount of unlocalized radioactivity. Normal tissue toxicity, especially to the bone marrow, has been the major limiting factor in the application of radioimmunotherapy to solid tumors. Pretargeting techniques provide an alternative method with which to obtain high selective tumor uptake of 90Y with simultaneous minimization of nontarget tissue background. METHODS. Current MoAb techniques employ either the biotin/avidin or the hapten/antibody system. DNA/DNA and prodrug/enzyme systems also have been used and many other ligand/receptor systems are possible. All the methods depend on a long circulating conjugate to obtain high target uptake with a diffusible, rapidly excreted effector molecule. RESULTS. Fast in, slow out tumor kinetics, ideal for therapy, have been achieved. In one mouse tumor system the biologic half-life of a bivalent 90Y JANUS tetraazacyclodidecanetetraacetic acid hapten, measured over 5 days, was approximately 24 hours. The therapeutic ratio, obtained from the integrated tumor and blood concentrations over 5 days, was approximately 20/1 compared with 2-3/1 with directly labeled MoAb. The total injected dose remaining in the mouse at 24 hours was 5.5%, 23% of which was in the tumor. CONCLUSIONS. These result suggest that it may be possible to deliver tumoricidal radiation doses with 90Y using pretargeting techniques without severe normal bone marrow irradiation.

Original languageEnglish (US)
Pages (from-to)2675-2680
Number of pages6
JournalCancer
Volume80
Issue number12 SUPPL.
StatePublished - Dec 15 1997

Keywords

  • Biotin- avidin
  • Hapten monoclonal antibody
  • Radioimmunodetection
  • Radioimmunotherapy
  • Yttrium-90

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Goodwin, D. A., & Meares, C. F. (1997). Pretargeting: General principles; October 10-12, 1996. Cancer, 80(12 SUPPL.), 2675-2680.