Quantification of [¹¹C]CURB PET using an irreversible reference tissue model with a cluster-derived pseudo-reference...

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Imaging
• Neuroscience

Background:

• Quantification of [11C]CURB, a positron emission tomography (PET) radiopharmaceutical for imaging fatty acid amide hydrolase (FAAH), traditionally requires invasive arterial sampling.
• Developing non-invasive methods is challenging due to the limitations of standard reference region models and the widespread expression of FAAH in the brain, complicating the identification of a ligand-free reference region.

Purpose of the Study:

• To introduce and validate the irreversible reference tissue model (IRTM) for non-invasive [11C]CURB quantification.
• To utilize a data-driven, clustering-based white matter (WM) region as a pseudo-reference region in conjunction with the IRTM.

Main Methods:

• Implemented the IRTM using a coupled-fit approach to estimate common parameters, yielding independent R₁ and k_f values.
• Quantification focused on macroparameters: R_i (relative net influx) and Rk₃ (relative trapping index).
• Validated the model against arterial input function (AIF)-based quantification using retrospective [11C]CURB PET data from 10 healthy participants, employing a clustering algorithm to define the WM pseudo-reference region.

Main Results:

• R_i proved to be a more robust metric than Rk₃, which exhibited high inter-subject variability.
• IRTM-derived R_i estimates demonstrated strong concordance with AIF-based measurements (R² = 0.96 for R_i and K_i; R² = 0.90 for λk₃).
• Voxel-wise parametric maps showed high image quality and signal-to-noise ratios at the individual subject level, despite potential biases from blood volume asymmetries identified in simulations.

Conclusions:

• A validated, fully non-invasive framework for [11C]CURB PET quantification has been established using the IRTM.
• The combination of IRTM with a data-driven WM pseudo-reference region achieves excellent agreement with AIF-based measurements.
• This approach supports the feasibility of non-invasive FAAH imaging using [11C]CURB PET.