Preparation and Bio-Evaluation of ⁹⁹Tc^m-Bicine/HYNIC-MPP2 as a Novel Agent for 5-HT_1A Receptor Imaging

The goal of this study is to develop a new ⁹⁹Tc^m-complex as a potential 5-HT_1A receptor imaging agent. Ligand HYNIC-MPP2, containing the MPP moiety was synthesized and labeled with technetium-99m. The ⁹⁹Tc^m-Bicine/HYNIC-MPP2 complex was prepared in high yield (>95% by TLC) with N,N-bis(2-hydroxyethyl)glycine (Bicine) as coligand at room temperature (RT) and it remained stable over 6 h at RT. ⁹⁹Tc^m-Bicine/HYNIC-MPP2 complex is neutral and hydrophilic， that were conformed by paper electrophoresis and octanol/water partition coefficient, respectively. In vivo biodistribution of ⁹⁹Tc^m-Bicine/HYNICMPP2 was investigated in normal mice. The result shows that this complex has moderate brain uptake (0.31%ID/g at 2 min post-injection（p.i.)）. The regional brain distribution and blocking studies show that its hippocampus uptake of ⁹⁹Tc^m-Bicine/HYNIC-MPP2 is the highest (1.00%ID/g at 2 min p.i.), while the cerebellum uptake is only 0.63%ID/g at 2 min p.i.. This is agreed with the distribution of 5-HT_1A receptor in the brain. After blocking with 8-OH-DPAT, the uptake of hippocampus is decreased obviously (0.42%ID/g), while the cerebellar uptake has no significant difference. The hippocampus/cerebellum uptake ratio is decreased from 1.59 to 0.89 after blocking. This result shows that ⁹⁹Tc^m-Bicine/HYNIC-MPP2 has specific binding to the 5-HT_1A receptor and it can be developed as a potential 5-HT_1A receptor imaging agent in the future.