Mapping human brain fatty acid amide hydrolase activity with PET

Area of Science:

• Neuroscience
• Radiochemistry
• Pharmacology

Background:

• Endocannabinoid system dysregulation is linked to neuropsychiatric disorders.
• Fatty acid amide hydrolase (FAAH) metabolizes anandamide, a key endocannabinoid.
• [(11)C]CURB is a novel PET tracer for imaging FAAH.

Purpose of the Study:

• To identify the optimal kinetic modeling approach for quantifying [(11)C]CURB binding to FAAH.
• To assess the reliability and scan duration for PET imaging of FAAH activity.

Main Methods:

• Six healthy volunteers underwent 90-minute PET scans with arterial blood sampling.
• Kinetic modeling was performed using one-tissue compartment model (TCM), 2-TCM (with/without irreversible trapping), and irreversible 3-TCM.
• Identifiability of kinetic parameters was assessed by coefficient of variation (COV).

Main Results:

• The 2-TCM with irreversible trapping demonstrated the best identifiability for PET outcome measures (K(i) and λk(3) COV <5%, k(3) COV <10%).
• Reducing scan time to 60 minutes did not impact the identifiability of rate constants.
• Regional cerebral blood flow showed minimal correlation with K(i), k(3), or λk(3).

Conclusions:

• The composite parameter λk(3) is sensitive to FAAH activity, making it suitable for PET quantification.
• The 2-TCM with irreversible trapping is the recommended model for [(11)C]CURB PET imaging of FAAH.
• [(11)C]CURB uptake is not primarily limited by cerebral blood flow in healthy subjects.