Highly Potent Fluorescent Multivalent Integrin Antagonists for Targeted Therapy and Imaging

In vivo fluorescence imaging of live U-87 xenograft tumor-bearing mice 24 hours post intravenously administered unconjugated Cy5.5 vs. bivalent IA-Cy5.5.



This invention presents a new class of fluorescent integrin ανβ3 antagonists that display higher binding affinity, specificity, and inherent stability than commercially available integrin antagonists.  Integrin ανβ3 has been shown to be involved in the formation of angiogenesis, a phenomenon that occurs in a variety of physiological and pathological processes, thereby making it an attractive target for the development of suitable candidates for imaging, diagnosis and/or therapy for one or more symptoms of diseases including cancer, osteoporosis, rheumatoid arthritis, and macular degeneration.



The finding that multivalent interactions produce higher biding affinity and specificity as compared to monovalent interactions has stimulated research into the design of new therapeutic and imaging agents. Current methods for developing multivalent ligands have proven to be inefficient; therefore, there is a need for the development of new methods that efficiently produce more potent multivalent ligands. 



  • A new highly efficient and accurate method for the design, synthesis and testing of more potent multivalent drug candidates that are useful for imaging as well as for treating one or more symptoms of cancer, inflammatory diseases, and autoimmune diseases.
  • The multivalent integrin ανβ3 ligands have over 100 fold the binding affinity of parent ligands resulting in significantly increased tumor cell uptake in vitro.
  • Multivalent integrin ανβ3 ligands have been shown to have higher specificity for the integrin ανβ3 receptor associated with tumors and an inherent stability not shown in commercially available ligands, resulting in increased tumor accumulation and retention in vivo.





Patent Application

PCT patent application filed.




Patent Information:
Licensing Contact
Belisa Diaz