Imaging Synaptic Vesicle Protein SV2C with ¹⁸F-UCB-F: An In Vitro Autoradiography and In Vivo NHP PET Study

Area of Science:

• Neuroscience
• Radiochemistry
• Molecular Imaging

Background:

• Synaptic vesicle glycoprotein 2C (SV2C) is implicated in Parkinson's disease (PD) and dopamine regulation.
• SV2C is a potential imaging target for PD synaptopathy.
• [18F]UCB-F was developed as a potential SV2C-binding radioligand.

Purpose of the Study:

• To evaluate the affinity and selectivity of [18F]UCB-F for SV2C.
• To assess the in vitro and in vivo properties of [18F]UCB-F in nonhuman primates (NHPs).

Main Methods:

• In vitro binding assays for SV2A, SV2B, and SV2C.
• In silico modeling of UCB-F binding.
• Autoradiography in rat and NHP brain tissues.
• Positron Emission Tomography (PET) studies in NHPs.

Main Results:

• [18F]UCB-F demonstrated specific binding in brain regions expressing SV2C in both rats and NHPs.
• [18F]UCB-F rapidly crossed the blood-brain barrier in NHPs but showed no clear regional distribution due to fast washout.
• In vitro studies indicated a temperature-dependent decrease in SV2C affinity, and in vivo studies showed rapid radiometabolism.

Conclusions:

• [18F]UCB-F is not a suitable PET radioligand for imaging SV2C in vivo.
• Rapid metabolism and reduced affinity at physiological temperatures limit its utility.
• Development of alternative SV2C imaging agents with improved stability and retention is necessary.