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.
ASJC Scopus subject areas
- Pharmaceutical Science