Synthesis and biological evaluation of 99mTc-HEDTA/HYNIC-MPP4 complex for 5-HT1A receptor imaging

Abstract

5-HT1A receptor is associated with a variety of pathophysiology of neuropsychiatric disorders. Accordingly, we have synthesized a new 5-HT1A receptor ligand (HYNIC-MPP4) and labeled it with 99mTc using N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA) as coligand. 99mTc-HEDTA/HYNIC-MPP4 was prepared under pH 6 at room temperature. Biodistribution of 99mTc-HEDTA/HYNIC-MPP4 in normal mice showed that this complex had moderate brain uptake (0.60% ID·g−1 at 2 min p.i.) and good retention. The hippocampus had the highest radioactivity uptake at 2 min p.i. (1.84% ID⋆g−1). The ratio of Hipp/CB was 3.1 at 2 min p.i. and increased to 4.4 at 60 min p.i. After blocking with 8-hydroxy-2-(dipropylamino) tetralin, the uptake of hippocampus was decreased significantly from 1.84% ID·g−1 to 0.53% ID·g−1 at 2 min p.i., while the cerebellum had no significant decrease. This 99mTc complex could be a potent agent for 5-HT1A receptor imaging.