There are a paucity of reliable serum and cerebrospinal (CSF) 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 which localizes to the desired target, allowing for visualization of the three dimensional distribution of the ligand's target receptor.~One of the upstream processes that are 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 (CSF1R) is found on microglia predominately in the brain, with low levels of expression in neurons and other neural cells, making it a promising target for studying microglial activation.~Given CSF1's 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 [5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide], is a positron-emitting, high-affinity ligand that is specific for CSF1R.~The aims of this study are as follows:~Establish the safety and tolerability of the [11C]CPPC PET radioligand in ALS patients and controls~Examine whether [11C]CPPC PET uptake is elevated in brains of ALS patients and whether there is a correlation with clinical phenotype.~Correlate [11C]CPPC PET imaging with other ALS outcome measures and biofluid biomarkers~Examine longitudinal changes in [11C]CPPC PET imaging during disease course.
Establish the safety and tolerability of the 5-cyano-N-(4-(4-[11C]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide ([11C]CPPC) PET radioligand in ALS patients and controls~Examine whether [11C]CPPC PET uptake is elevated in brains of ALS patients and whether there is a correlation with clinical phenotype.~Correlate [11C]CPPC PET imaging with other ALS outcome measures and biofluid biomarkers~Examine longitudinal changes in [11C]CPPC PET imaging during disease course.