First evaluation in multiple sclerosis using PET tracer [¹⁸F]3F4AP demonstrates heterogeneous binding across lesions

Area of Science:

• Neuroimaging
• Radiochemistry
• Neurology

Background:

• Multiple sclerosis (MS) involves demyelination and axonal loss in the central nervous system.
• Conventional MRI lacks specificity in differentiating MS lesions based on axonal integrity.
• Novel imaging tracers are needed to assess myelin and axonal status in MS.

Purpose of the Study:

• To evaluate the potential of [¹⁸F]3F4AP, a novel positron emission tomography (PET) tracer, for insights into demyelination in multiple sclerosis.
• To assess the tracer's ability to distinguish between demyelinated lesions with different axonal integrity.
• To explore [¹⁸F]3F4AP as a tool for monitoring MS progression and therapy response.

Main Methods:

• Three individuals with MS and three healthy controls underwent dynamic PET scanning with [¹⁸F]3F4AP and 3T MRI.
• MRI sequences included MPRAGE, FLAIR, and Myelin Water Imaging (MWI).
• Kinetic modeling (2TCM, Logan analysis) was used to assess tracer kinetics, delivery, and binding in brain regions and lesions, comparing PET findings with MRI and myelin content.

Main Results:

• [¹⁸F]3F4AP demonstrated 14% higher accumulation in gray and white matter in MS patients compared to controls.
• Tracer kinetics were well-described by a two-tissue compartmental model (2TCM), with good correlation between Logan analysis V_T and late SUV images.
• Lesions showed variable tracer binding, suggesting [¹⁸F]3F4AP can differentiate lesions with differing axonal integrity, despite similar MRI appearances.

Conclusions:

• [¹⁸F]3F4AP exhibited good reproducibility and identified differences between MS patients and controls.
• The tracer's heterogeneous binding across lesions indicates its potential to differentiate lesions with and without axonal integrity.
• [¹⁸F]3F4AP may be valuable for monitoring MS progression and evaluating remyelination therapies.