Liver uptake of radiolabeled targeting proteins and peptides: considerations for targeting peptide conjugate design

Radionuclide imaging of molecular targets for cancer therapy is likely to be a powerful tool for patient stratification and response monitoring, allowing more personalized cancer treatment. Radiolabeled proteins and peptides are a promising class of imaging probes for visualization of molecular targets in vivo. However, hepatic uptake and hepatobiliary excretion of radioactivity can decrease imaging contrast, reducing the detection sensitivity of hepatic and extrahepatic abdominal metastases, respectively. In this article, we review factors that influence the hepatic uptake of radioactivity (e.g. the chemical nature of radiocatabolites and physicochemical properties of targeting peptides and linkers) to provide input for the rational design of peptide-based imaging probes.