Quantitative Spatial Profiling of Antibody Delivery and Target Engagement Using Optically Labeled Antibodies

Hidenori Tanaka1, Georgii Vasiukov2, Candace J Grisham2

  • 1Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee hidenori.tanaka@vumc.org e.rosenthal@vumc.org.

Insights

This study introduces a new method to visualize drug distribution in human tumors, enabling single-cell analysis of therapeutic antibody delivery and pharmacodynamics in formalin-fixed, paraffin-embedded tissues.

Area of Science:

  • Oncology
  • Biomedical Imaging
  • Pharmacology

Background:

  • Visualizing drug distribution in human tumors is essential for optimizing biologic therapeutics.
  • Current clinical methods struggle to colocalize drugs and biomarkers on the same tissue section.
  • Accurate visualization is key for understanding drug pharmacodynamics and efficacy.

Purpose of the Study:

  • To develop a reproducible workflow for visualizing drug distribution and biomarker colocalization in human tumors.
  • To enable quantitative, single-cell analysis of therapeutic antibody delivery and pharmacodynamics.
  • To overcome limitations of current clinical workflows in analyzing drug-tissue interactions.

Main Methods:

  • Integration of near-infrared imaging of optically labeled antibodies with multiplex immunostaining.
  • Utilizing computational registration for precise spatial alignment of imaging data.
  • Development of a reproducible workflow for analyzing formalin-fixed, paraffin-embedded (FFPE) tissue sections.

Main Results:

  • Demonstrated heterogeneous accumulation of panitumumab-IRDye800CW in epidermal growth factor receptor-positive tumor regions.
  • Quantified drug penetration gradients in relation to tumor architecture.
  • Enabled single-cell level analysis of drug distribution and target engagement.

Conclusions:

  • Established a multiplex imaging platform for analyzing therapeutic antibody delivery in FFPE human tumors.
  • The platform facilitates single-cell analysis of drug pharmacodynamics and delivery.
  • This approach enhances the understanding of biologic therapeutic distribution and efficacy in oncology.