Metal Ion Complexes for Antibody Imaging and Therapy in Breast Cancer

Abstract

The goals of this project were to prepare and test novel bifunctional chelates based on DOTA to anti-CEA and anti-her2/neu antibodies. The conjugates were labeled with In-111 for imaging and Y-90 for therapy. Two tumor xenograft models were tested: MCF7 cell transfected with her2/neu for over-expression of her2/neu, and MCF7 cell expressing "normal" amounts of her2/neu. Both cell lines also express CEA. We showed that both models had good uptake of In-111 labeled antibodies and responded to Y-90 labeled RIT. The RIT response was further improved by the combined administration of taxol and RIT. Novel peptide-DOTA conjugates to recombinant antibody fragments were prepared, radiolabeled with In-111, and shown to reduce normal kidney uptake compared to DOTA directly conjugated to the same antibody fragments. This work demonstrates that breast cancers can be treated with both anti-her2/neu and anti-CEA antibodies, and that recombinant antibody fragments can be used for imaging or therapy with the novel peptide linker chelators.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2002
Accession Number
ADA404911

Entities

People

  • John E. Shively

Tags

DTIC Thesaurus Topics

  • Albumins
  • Alkanes
  • Antibodies
  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Mass Spectrometry
  • Medical Personnel
  • Neoplasms
  • Organic Chemistry
  • Ovarian Cancer
  • Proteins
  • Sulfur Compounds

Fields of Study

  • Biology

Readers

  • Molecular and Cellular Biochemistry
  • Oncology (Cancer Research).