Our main goal is to develop new radioligands for dopamine, muscarinic acetylcholine, serotonin, transporters, cocaine, CRH, and sigma receptors in the brain to be used for neuroimaging and the clinical routine patient studies by SPECT and PET. Our interest is to apply these radiotracers to study the changes in receptor function in Alzheimer’s disease, Parkinsons disease, Tourette syndrome, schizophrenia, and alcoholism. During this period we had a collaborative effort with Dr. Kenner Rice , NIH, Dr. William C Eckelman, NIH, Dr. Richard Glennon, University of Virginia , school of medicine, Dr. Lei Zhang, NIMH, and Dr. Daniel W. McPherson, Oak Ridge National Laboratory. We were working to develop radioligands for receptors such as CRH, selective Muscarinic M-2, and serotonin (5HT2A/2C) for SPECT and PET imaging and the production of radioisotope, Br-76 using for PET imaging. We can summarized our research as follows: 1. We have developed a better CRH radioligand than last year. This radioligand can provide a high affinity and selectivity to CRH receptors. The radiochemical yield for this radioligand was 70% when it was radiolabelled with I-123 for 5 minutes at room temperature. Initial In vitro study indicated that this radioligand bound to the CRH receptor region in the brain. 2. We have also developed radiobromination method for serotonin 5HT2A/5HT2C radioligand for PET. This radioligand could provide a high affinity and selectivity to serotonin receptors. This radiolignad, [76Br] –DOB, has been radiobromination successfully and the radiochemical yield for this radioligand was 70% when it was radiolabelled with Br-76 for 15 minutes at 45oC. This radiotracer has been applied to monkey study in vivo. 3. We have also developed a selective Muscarinic M-2 receptor radioligand, QNP, which provided a high affinity and selectivity to the M-2 receptors in vivo. The radiochemical yield for this ligand was 70% when it was radiolabelled with I-123 for 5 minutes at room temperature. 4. Collaboration with Dr. Eckelman from the PET imaging group, we were able to prepare Br-76, positron emitter with a half-lives of 16 hour. Thus, it will be very useful to convert our radioligands to Br-76 since the PET imaging can provide a high resolution and better imaging than SPECT. 5. 123I-BZM radiligands was prepared to use to monitor the effect of a new drug, clozaprexin ( an analog of clozapine), in D-2 receptors in the monkey’s brain in vivo by SPECT. 6. Collaboration with Dr. Zhang , we were able to study the different kind of receptors concentration in the region of the early brain development using the above radiotracers. - SPECT, IBZM, IQNB, BCIT, radiotracer, Br-76, PET, dopamine, serotonin, muscarinic, receptors
| Heinz, A; Goldman, D; Jones, D W et al. (2000) Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 22:133-9 |
