Non-invasive estimation of [¹¹C]PBR28 binding potential

Area of Science:

• Neuroimaging
• Radiochemistry
• Molecular Imaging

Background:

• [11C]PBR28 is a PET radioligand for in vivo translocator protein (TSPO) density estimation.
• Quantification typically requires arterial blood sampling due to the absence of a suitable reference region.
• Simultaneous estimation (SIME) offers a method for kinetic modeling without a reference region.

Purpose of the Study:

• To evaluate a SIME methodology for [11C]PBR28 PET data quantification.
• To assess if SIME can detect group differences in TSPO densities without arterial blood samples, using template input functions (tIFs).
• To compare the sensitivity of SIME with tIFs against standard kinetic modeling.

Main Methods:

• Utilized [11C]PBR28 PET and arterial plasma data from 21 Alzheimer's disease (AD) patients and 15 controls.
• Applied SIME with both measured arterial input functions (AIFs) and template input functions (tIFs).
• Compared regional binding potential (BPND) estimates and effect sizes between methods, including standard kinetic modeling.

Main Results:

• SIME with tIFs yielded BPND estimates highly comparable to those with AIFs (3.0 ± 21% difference, r² = 0.78).
• SIME with tIFs demonstrated significant differences in TSPO densities between AD patients and controls (31.0%, p=0.004), outperforming standard kinetic modeling (16.1%, p=0.12).
• No significant TSPO binding differences were detected in the cerebellum across methods.

Conclusions:

• SIME is a viable method for estimating [11C]PBR28 binding potential (BPND) in clinical studies.
• Arterial blood sampling may be unnecessary for [11C]PBR28 quantification if reliable tIFs can be established.
• This approach enhances the utility of [11C]PBR28 PET for investigating neuroinflammation in conditions like Alzheimer's disease.