# Labeling of Bruton’s Tyrosine Kinase (BTK) Inhibitor [11C]BIO-2008846 in Three Different Positions and Measurement in NHP Using PET

## TL;DR

This study used PET imaging to track a BTK inhibitor in non-human primate brains, showing it spreads evenly but binds minimally to specific sites.

## Contribution

The study introduces a radiolabeled BTK inhibitor for PET imaging and evaluates its brain distribution in NHPs.

## Key findings

- The radiolabeled BTK inhibitor showed homogeneous brain distribution in NHPs.
- Brain uptake ranged from 1.8% to 3.2% ID, with minimal specific binding observed.
- Radiometabolite analysis showed 10% unchanged radioligand after 30 minutes.

## Abstract

Bruton’s tyrosine kinase (BTK) is pivotal in B-cell signaling and a target for potential anti-cancer and immunological disorder therapies. Improved selective reversible BTK inhibitors are in demand due to the absence of direct BTK engagement measurement tools. Promisingly, PET imaging can non-invasively evaluate BTK expression. In this study, radiolabeled BIO-2008846 ([11C]BIO-2008846-A), a BTK inhibitor, was used for PET imaging in NHPs to track brain biodistribution. Radiolabeling BIO-2008846 with carbon-11, alongside four PET scans on two NHPs each, showed a homogeneous distribution of [11C]BIO-2008846-A in NHP brains. Brain uptake ranged from 1.8% ID at baseline to a maximum of 3.2% post-pretreatment. The study found no significant decrease in regional VT values post-dose, implying minimal specific binding of [11C]BIO-2008846-A compared to free and non-specific components in the brain. Radiometabolite analysis revealed polar metabolites with 10% unchanged radioligand after 30 min. The research highlighted strong brain uptake despite minor distribution variability, confirming passive diffusion kinetics dominated by free and non-specific binding.