Non-invasive modelling and parametric methods for quantification of MAO-B activity using [¹¹C]L-deprenyl-D2 PET

Area of Science:

• Neuroimaging
• Radiochemistry
• Pharmacokinetics

Background:

• The PET radioligand [¹¹C]L-deprenyl-D2 targets monoamine oxidase B (MAO-B), crucial for studying neuroinflammation in neurological disorders.
• Accurate quantification of MAO-B activity using [¹¹C]L-deprenyl-D2 PET is essential for reliable diagnostic and research applications.

Purpose of the Study:

• To evaluate the accuracy of non-invasive and parametric quantification methods for [¹¹C]L-deprenyl-D2 PET.
• To compare different kinetic modeling approaches, including reference tissue methods and a specific binding index (SBI), against a gold standard arterial input function.

Main Methods:

• Twenty-eight subjects underwent dynamic 60-minute [¹¹C]L-deprenyl-D2 PET scans.
• Quantification was performed using an irreversible two-tissue compartment model (2T3k) with plasma input, reference tissue models (cerebellum), and SBI.
• Parametric images were generated using basis function implementation of 2T3k, reference Patlak, and reduced reference tissue models.

Main Results:

• Parametric images of the irreversible binding parameter λk₃ derived from the 2T3k model showed good agreement with VOI-based nonlinear regression.
• Non-invasive methods, including modified cerebellar reference models and SBI, exhibited poor-to-moderate correlations with arterial input-based analysis.
• Voxel-wise group comparisons using non-invasive methods revealed false positive differences in MAO-B activity.

Conclusions:

• Full kinetic analysis with an arterial input function is indispensable for accurate MAO-B activity assessment using [¹¹C]L-deprenyl-D2 PET.
• Non-invasive quantification strategies, such as reference tissue models and SBI, are not sufficiently reliable for precise MAO-B quantification and may lead to erroneous conclusions in group analyses.
• The study underscores the necessity of robust kinetic modeling for advancing neuroinflammation research with [¹¹C]L-deprenyl-D2 PET.