Multivalent Probes in Molecular Imaging: Reality or Future?

Multivalency is a powerful tool to increase the binding affinity of ligands, and this can greatly enhance image performance in molecular imaging modalities. Successful translation of multivalent molecular imaging agents (MMIAs) requires careful design of the core and selection of the best possible ligand–linker combination through understanding their binding properties. Rational design of MMIAs often neglects several key aspects, including the choice of the multivalent scaffold, its ligand-availability, and its dependencies on physiological conditions and biological barriers. Achieving high imaging performance of MMIAs imposes additional considerations compared with monovalent molecules because of their size, steric factors, and pharmacokinetic properties. The rapidly developing field of molecular medical imaging focuses on specific visualization of (patho)physiological processes through the application of imaging agents (IAs) in multiple clinical modalities. Although our understanding of the principles underlying efficient IAs design has increased tremendously, many IAs still show poor in vivo imaging performance because of low binding affinity and/or specificity. These limitations can be addressed by taking advantage of multivalency, in which multiple copies of a ligand are employed to strengthen the interaction. We critically address specific challenges associated with the application of multivalent compounds in molecular imaging, and we give directions for a stepwise approach to the design of multivalent imaging probes to improve their target binding and pharmacokinetics (PK) for improved diagnostic potential. The rapidly developing field of molecular medical imaging focuses on specific visualization of (patho)physiological processes through the application of imaging agents (IAs) in multiple clinical modalities. Although our understanding of the principles underlying efficient IAs design has increased tremendously, many IAs still show poor in vivo imaging performance because of low binding affinity and/or specificity. These limitations can be addressed by taking advantage of multivalency, in which multiple copies of a ligand are employed to strengthen the interaction. We critically address specific challenges associated with the application of multivalent compounds in molecular imaging, and we give directions for a stepwise approach to the design of multivalent imaging probes to improve their target binding and pharmacokinetics (PK) for improved diagnostic potential. the ratio of the target concentration (Bmax) to the equilibrium dissociation constant (Kd) of the IA: BP = Bmax:Kd kB = 1.38065 × 10−23 J.K−1 prefactor that includes the fact that a multivalent molecule has Ω1 distinguishable interactions and not only one. defined as C(target) * C(ligand) / C(ligand-target complex) [t) × (ligand] (ligand–t). a measure of radioactivity – the time required for half of the radioactivity to decay. expresses the lipophilicity of molecules. The most common method for determining logP is by the water/n-octanol distribution method at room temperature, in which the concentration (C) of the molecule is determined in each phase, and logP = log(Coctanol/Cwater). defined as moles of the target receptor per gram of tissue. an inhibitor of tumor angiogenesis and tumor cell proliferation.