Synthesis and autoradiographical evaluation of novel high-affinity Tc-99m ligands for the serotonin 5-HT1A receptor


Synthesis and autoradiographical evaluation of novel high-affinity Tc-99m ligands for the serotonin 5-HT1A receptor

Drews, A.; Heimbold, I.; Varnäs, K.; Hall, H.; Halldin, C.; Pietzsch, H.-J.; Syhre, R.; Seifert, S.; Brust, P.; Johannsen, B.

Despite tremendous effort in the development of Tc-99m complexes to image post-synaptic CNS receptors, various attempts failed so far (1). The combination of sufficient brain uptake and high affinity to the receptors (IC50 < 1 nM) seems to be crucial. Our studies are focused on complexes for serotonin 5-HT1A and 5-HT2A receptors. Recently we succeeded in synthesizing of complex I, which is a high affinity Tc-99m ligand for the 5-HT1A receptor derived from the well known serotonin 5-HT1A antagonist WAY 100635 and shows a subnanomolar affinity (0.13 nM) and a brain uptake of 0.20 % ID in rats, 5 min post injection (2). Figure 1 shows the structure of the complex I.

Here we report on the synthesis of new high-affinity Tc-99m ligands for the 5-HT1A receptor with improved brain uptakes. The complexes are evaluated in receptor binding assays, by in vitro autoradiography in post mortem human brain and by in vivo studies.

Keywords: serotonin 5-HT1A receptor; Tc-99m receptor ligand; receptor binding assay; in vitro autoradiography

  • Poster
    14th International Symposium on Radiopharmaceutical Chemistry, Interlaken/Schweiz, 10.-15.06.2001
  • Abstract in refereed journal
    J. Labelled Cpd. Radiopharm. 44, Suppl. 1 (2001), S544-S546

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Publ.-Id: 3874