High-Throughput Approaches to the Development of Molecular Imaging Agents.
Molecular imaging allows for the visualization of changes at the cellular level in diseases such as cancer. A successful molecular imaging agent must rely on disease-selective targets and ligands that specifically interact with those targets. Unfortunately, the translation of novel target-specific ligands into the clinic has been frustratingly slow with limitations including the complex design and screening approaches for ligand identification, as well as their subsequent optimization into useful imaging agents. This review focuses on combinatorial library approaches towards addressing these two challenges, with particular focus on phage display and one-bead one-compound (OBOC) libraries. Both of these peptide-based techniques have proven successful in identifying new ligands for cancer-specific targets and some of the success stories will be highlighted. New developments in screening methodology and sequencing technology have pushed the bounds of phage display and OBOC even further, allowing for even faster and more robust discovery of novel ligands. The combination of multiple high-throughput technologies will not only allow for more accurate identification, but also faster affinity maturation, while overall streamlining the process of translating novel ligands into clinical imaging agents.
Department of Biomedical Engineering, University of California Davis, Davis, CA, USA.
Lina Y
LY
Hu
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.|Robert M. Berne Cardiovascular Research Center, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Kimberly A
KA
Kelly
Department of Biomedical Engineering, University of California Davis, Davis, CA, USA. jlsutcliffe@ucdavis.edu.|Department of Internal Medicine, Division of Hematology Oncology, University of California, Davis, Sacramento, CA, USA. jlsutcliffe@ucdavis.edu.|Center for Molecular and Genomic Imaging, University of California, Davis, Davis, CA, USA. jlsutcliffe@ucdavis.edu.
Julie L
JL
Sutcliffe
D000595:Amino Acid Sequence; D000818:Animals; D020650:Combinatorial Chemistry Techniques; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D007202:Indicators and Reagents; D057054:Molecular Imaging / Q000379:methods*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry
D007202:Indicators and Reagents; D019151:Peptide Library; D010455:Peptides
Combinatorial library; High-throughput; Molecular imaging; OBOC; Peptides; Pet; Phage display