Post-mortem human brain autoradiography of the norepinephrine transporter using (S,S)-[18F]FMeNER-D2

Area of Science:

• Neuroscience
• Radiochemistry
• Pharmacology

Background:

• The norepinephrine transporter (NET) plays a crucial role in regulating neurotransmission.
• Developing selective radioligands for NET is essential for in vivo brain imaging and research.

Purpose of the Study:

• To characterize the in vitro binding of the novel radioligand (S,S)-[18F]FMeNER-D2 in human post-mortem brain tissue.
• To assess the selectivity and distribution of norepinephrine transporter binding.

Main Methods:

• Whole hemisphere autoradiography was performed on human post-mortem brain tissue.
• Binding affinity and distribution were analyzed using the radioligand (S,S)-[18F]FMeNER-D2.
• NET-selectivity was confirmed through co-incubation with known NET inhibitors like desipramine.

Main Results:

• The highest density of radioligand binding was observed in the locus coeruleus.
• Moderate binding was found in the cortex, cerebellum, and thalamus.
• Lower binding occurred in the caudate and putamen.
• Desipramine confirmed the NET-selective binding of the radioligand.
• Duloxetine, a dual NET/SERT inhibitor, inhibited binding, while PE2I and citalopram did not.

Conclusions:

• (S,S)-[18F]FMeNER-D2 demonstrates high affinity and selectivity for the norepinephrine transporter in human brain.
• The radioligand exhibits a distinct distribution pattern, with highest density in the locus coeruleus.
• These findings support the potential utility of (S,S)-[18F]FMeNER-D2 for positron emission tomography (PET) imaging of the norepinephrine transporter system.