New approaches to delivering metal-labeled antibodies to tumors: Synthesis and characterization of new biotinyl chelate conjugates for pre-targeted diagnosis and therapy

Oliver Renn, David A. Goodwin, Martin Studer, Justin K. Moran, Vincent Jacques, Claude F. Meares

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Radiolabeled monoclonal antibodies are widely used in the detection and treatment of cancer. However, several problems still prevent full clinical exploitation of these reagents. Low tumor/background ratios in immunoscintigraphy and high background radioactivity in therapy are limiting factors. The strategy of pre-targeting may overcome these limitations. One of the strategies is based on the avidin-biotin system. The use of biotinylated antitumor antibodies, followed by avidin and then by a biotin-chelate conjugate in a three step procedure to image cancer sites has been demonstrated (G, Paganelli el al., Cancer Res. 51 (1991) 5960-5966). In this report we describe the synthesis of several biotin-chelate conjugates. Among these chelate conjugates, biotinyl-LC-DOTA binds the diagnostic and therapeutic radiometals 111indium, 90yttrium and67 copper with the required stability and has excellent physiological properties for pre- targeted diagnosis and therapy. Biotinyl-LC-DOTA can be prepared from 2-p- nitrobenzyl-DOTA via p-aminobenzyl-DOTA and 6-((biotinyl)amino)caproic acid (biotin X) in a simple two-step synthesis in 90% yield.

Original languageEnglish (US)
Pages (from-to)239-249
Number of pages11
JournalJournal of Controlled Release
Volume39
Issue number2-3
DOIs
StatePublished - May 1996

Keywords

  • DOTA
  • Indium-111
  • Radioimmunoimaging
  • Radioimmunotherapy
  • Yttrium-90

ASJC Scopus subject areas

  • Pharmaceutical Science

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