Biodistribution of [125I]-labeled therapeutic proteins: application in protein drug development beyond oncology

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Preclinical Biologics Development
• Translational Medicine

Background:

• Current biodistribution studies predominantly focus on tumor-targeting agents.
• There is a need to highlight the utility of biodistribution for non-oncology biotherapeutics.
• Methodological perspectives for these studies are essential for preclinical development.

Purpose of the Study:

• To demonstrate the value of biodistribution studies in preclinical development for non-oncology indications.
• To provide practical insights into the methodology of biodistribution studies for biotherapeutics.
• To explore the application of biodistribution for various classes of protein compounds.

Main Methods:

• Case studies illustrating biodistribution analysis in preclinical biotherapeutic development.
• Comparative analysis of biodistribution profiles for different biologics, including human monoclonal antibodies.
• Temporal biodistribution profiling to assess kinetics and reversibility of accumulation.

Main Results:

• Biodistribution profiles can be compared within biologic classes to identify unexpected off-target uptake.
• Temporal data reveals kinetics and reversibility of target- and off-target accumulation.
• Tissue data offers insights into exposure at therapeutic or toxic sites, especially with anti-product antibody formation.

Conclusions:

• Biodistribution studies are vital for assessing in vivo disposition of biotherapeutics across diverse indications.
• These studies aid in understanding drug exposure, target engagement, and potential toxicities.
• Biodistribution analysis is a valuable tool for both existing and novel protein-based therapeutics.