Our main goal is to develop new radioligands to be used for neuroimaging and the clinical routine patient studies by single photon emission computed tomography, (SPECT). We are still involved in a collaborative effort with NIDDKD in Bethesda with two different laboratories : Dr. Kenner Rice and Dr. Kenneth A. Jacobson to develop ligands for neuroimaging by SPECT. During this period, we are also in a collaboration with Dr. Innis in Yale University to study the diazepam-insensitive receptors using our diazepam- insensitive ligand. This ligand is almost exclusively localized to the cerebellum in CNS and has been linked to antagonize biochemical and behavioral effects of ethanol. The collaboration with Dr. Bowen is to study the sigma subtypes using our sigma ligands and the collaboration with Dr. Zeeberg is to study the autoradiography in rats using [I- 125]IQNB. During this period, we developed two new ligands for opioid receptors with the high affinity and selectivity to mu and delta subtypes respectively. Radioiodination methods with high radiolabelling yield were developed for these ligands. The radiochemical yield for these ligands was > 70% for 5 minutes at room temperature. SPECT imaging in primates were performed using these ligands. 125I or 123I-sigma ligands were prepared for binding assays, tissue culture studies, and SPECT imaging in primates in order to further the understanding of the ligands. 125IQNB and 123IQNB have been prepared using the tributylstannyl precursor for our new radiolabelling method. Four sterioisomers of radioactive IQNB have been prepared for SPECT imaging and autoradiography studies. This 123IQNB preparation method is simple, rapid, high radiolabelling yield, and save more than 50% of the cost for buying I- 123. Normal volunteers and Alzheimer's disease patients have been studied using 123IQNB. The result indicated that the receptor concentrations were different between the normal volunteers and the patients with disease. 123IQNB and 123IBZM ligands were prepared to study the muscarinic receptors and D-2 receptors of patients routinely by SPECT.