Deciphering albumin-directed drug delivery by imaging

Abstract

Albumin is the most abundant plasma protein, exhibits extended circulating half-life, and its properties have long been exploited for diagnostics and therapies. Many drugs intrinsically bind albumin or have been designed to do so, yet questions remain about true rate limiting factors that govern albumin-based transport and their pharmacological impacts, particularly in advanced solid cancers. Imaging techniques have been central to quantifying - at a molecular and single-cell level - the impact of mechanisms such as phagocytic immune cell signaling, FcRn-mediated recycling, oncogene-driven macropinocytosis, and albumin-drug interactions on spatial albumin deposition and related pharmacology. Macroscopic imaging of albumin-binding probes quantifies vessel structure, permeability, and supports efficiently targeted molecular imaging. Albumin-based imaging in patients and animal disease models thus offers a strategy to understand mechanisms, guide drug development and personalize treatments.

Keywords: Blood-brain barrier (BBB); Human serum albumin (HSA); Intravital microscopy; Magnetic resonance imaging (MRI); Nanoparticulate albumin bound paclitaxel (nab-paclitaxel); Positron emission tomography (PET); Secreted protein acidic and rich in cysteine (SPARC); Single-photon emission computed tomography (SPECT).