1. 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 2. Examine whether \[11C\]CPPC PET uptake is elevated in brains of ALS patients and whether there is a correlation with clinical phenotype. 3. Correlate \[11C\]CPPC PET imaging with other ALS outcome measures and biofluid biomarkers 4. Examine longitudinal changes in \[11C\]CPPC PET imaging during disease course.
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: 1. Establish the safety and tolerability of the \[11C\]CPPC PET radioligand in ALS patients and controls 2. Examine whether \[11C\]CPPC PET uptake is elevated in brains of ALS patients and whether there is a correlation with clinical phenotype. 3. Correlate \[11C\]CPPC PET imaging with other ALS outcome measures and biofluid biomarkers 4. Examine longitudinal changes in \[11C\]CPPC PET imaging during disease course.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Radioactive PET ligand to determine microglia expression of colony stimulating factor 1 receptor (CSF1R).
Safety of use of [11C]CPPC in patients with ALS as assessed by adverse events
Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with a diagnosis of ALS. Safety will be assessed by number of adverse events during and up to 180 days after the injection
Time frame: Up to 180 days after scan
Safety of use of [11C]CPPC in patients with ALS as assessed by a change in neurological status
Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with a diagnosis of ALS. Safety will be assessed by neurological physical exam to determine if there is a change in the findings from baseline.
Time frame: Baseline and 180 days after scan
Safety of use of [11C]CPPC in patients with ALS as assessed by a change in complete blood count (CBC) test
Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with a diagnosis of ALS. Safety will be assessed by monitoring of the complete blood count (CBC) for a change from baseline that is outside of the normal range.
Time frame: Baseline and 180 days after scan
Safety of use of [11C]CPPC in patients with ALS as assessed by a change in complete metabolic panel (CMP) test
Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with a diagnosis of ALS. Safety will be assessed by a change in the CMP from baseline that is outside of the normal range.
Time frame: Baseline and 180 days after scan
Sensitivity of use of [11C]CPPC as assessed by a radiologist
Sensitivity of use of \[11C\]CPPC in PET neuroimaging to detect ALS will be determined by comparing the PET images from patients with ALS with those from healthy controls.
Time frame: Up to 180 days after scan
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Masking
NONE
Enrollment
20