⁸⁹Zr-Immuno-PET with Immune Checkpoint Inhibitors: Measuring Target Engagement in Healthy Organs

Area of Science:

• Immunology
• Nuclear Medicine
• Pharmacology

Background:

• 89Zr-immuno-PET visualizes monoclonal antibody (mAb) biodistribution targeting the immune system.
• Uptake measurements include specific and non-specific components, influenced by tracer plasma availability.
• Assessing target engagement requires differentiating specific uptake from non-specific binding.

Purpose of the Study:

• To evaluate target engagement of five immune checkpoint-targeting 89Zr-labeled mAbs.
• To compare mAb uptake with established non-specific baseline values.
• To investigate saturation effects with increasing mAb mass doses.

Main Methods:

• Analyzed 89Zr-immuno-PET data from five mAbs (anti-PD-1, anti-PD-L1, anti-LAG-3, anti-CTLA-4) in 35 patients.
• Quantified irreversible uptake (Ki) using Patlak analysis, accounting for plasma activity.
• Compared Ki values to non-specific baseline Ki values and assessed dose-dependent effects.

Main Results:

• Most mAbs showed target engagement in spleen (Ki above baseline, decreasing with dose).
• Similar patterns observed in bone marrow; kidney uptake was generally within baseline, with some saturation at high doses.
• Brain uptake was negligible for all mAbs and doses.

Conclusions:

• Patlak analysis and non-specific baseline values provided evidence for target engagement of several immune checkpoint inhibitors in lymphoid organs.
• Decreasing Ki values with increasing mass doses validate Patlak analysis for assessing target engagement of PET ligands with irreversible uptake.