Synthesis and Autoradiographic Evaluation of a Novel High-Affinity Tc-99m Ligand for the 5-HT_2A Receptor

The successful development of [^99mTc]TRODAT as ligand for the dopamine transporter has shown the feasibility to image specific transporters in the brain with radiotracers based on Tc-99m (1). In contrast to this achievement and despite the efforts many groups have devoted so far, the search for Tc-99m complexes with affinity to post-synaptic CNS receptors have not yet reached the same stage of development (2). As one of the consequences for the design of serotonin-5-HT_2A receptor binding Tc-99m complexes an affinity of < 1nM is believed to be a prerequisite for further progress. Aiming at such a high affinity, we have pursued our design concept starting from ketanserin as lead structure for 5-HT_2A receptor binding ligands (3, 4).
Here we report on the synthesis of a new high-affinity Tc-99m ligand that meets the requirement of picomolar affinity. The complex is evaluated in various receptor binding assays and by in vitro autoradiography.