Physicochemical Descriptors in Biodistribution and Clearance of Contrast Agents

Abstract

Hepatobiliary and renal excretions are the two major in vivo elimination pathways, of which prediction is particularly important for the optimization of systemic and/or target‐site exposure of new near‐infrared (NIR) fluorescent contrast agents. To characterize the physicochemical descriptors associated with each clearance route, a compound library containing more than 760 NIR fluorophores is analyzed and systematically reviewed in this study. Although there are a host of biochemical and physiological mechanisms that ultimately determine the in vivo fate of any given molecule, the physicochemical properties of contrast agents including molecular weight, hydrophobicity, topological polar surface area, molecular charges, and hydrogen/rotatable bonds are often indicative of each clearance route. The approach developed is anticipated to be useful in early lead identification studies when selecting NIR fluorescent contrast agents from large database screenings. It may also be applied to prioritize synthetically feasible chemical modifications during lead compound optimization.

Keywords

• biodistribution
• contrast agents
• machine learning
• molecular descriptors
• physicochemical properties