[18F]RS-127445 radiosynthesis and evaluation as a 5-HT2B receptor PET radiotracer in rat brain

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter involved in many physiological and pathological mechanisms through its numerous receptors. Among these, the 5-HT_2B receptor is known to play a key role in multiple brain disorders but remains poorly understood. Positron emission tomography (PET) can contribute to a better understanding of pathophysiological mechanisms regulated by the 5-HT_2B receptor. To develop the first PET radiotracer for the 5-HT_2B receptor, RS-127445, a well-known 5-HT_2B receptor antagonist, was labeled with fluorine-18. [¹⁸F]RS-127445 was synthesized in a high radiochemical purity and with a good molar activity and radiochemical yield. Preliminary PET scans in rats showed good brain penetration of [¹⁸F]RS-127445. However, competition experiments and in vitro autoradiography showed high non-specific binding, especially to brain white matter.