Development of [11C]CPPC as a Clinical PET Radioligand Biomarker of Microglial Activation in ALS
Abstract
There are a paucity of reliable biomarkers and validated neuroimaging techniques to aid in amyotrophic lateral sclerosis (ALS) diagnosis, prognosis, or pharmacodynamic insight. Positron emission tomography (PET) imaging is a technique that uses radioactive molecules attached to a ligand of interest allowing for visualization of the 3D distribution of the ligands target receptor. One of the upstream processes thought to lead to motor neuron degeneration in ALS is microglial dysfunction, resulting in the initiation of neuroinflammatory cascades. Macrophage colony stimulating factor 1 receptor is found on microglia with low levels of expression in neurons and other neural cells, making it a promising target for studying microglial activation. Given CSF1s potential role in ALS disease progression, and that its receptor (CSF1R) can be directly targeted, ligands binding this receptor are an area of interest for imaging in ALS. [11C]CPPC, is a positron-emitting, high-affinity ligand that is specific for CSF1R. [11C]CPPC demonstrates high and specific brain uptake in postmortem human tissue from control patients and those with other neurodegenerative diseases. We will establish the utility of [11C]CPPC PET as a measure of neuroinflammation, specifically microglial activation, and to correlate this activity with other clinical and biofluid measures of disease progression in ALS.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1219045
Entities
People
- Nicholas J Maragakis
Organizations
- Johns Hopkins University