Our main goal is to develop radioligands for dopamine, muscarinic acetylcholine, serotonin, dopamine and serotonin transporters, cocaine, nicotine, benzodiazapine, CRH, glutamate, and sigma receptors to be used for neuroimaging for research and clinical routine patient studies by SPECT or PET because these receptors play a main role for controlling the mental status in patients. We have applied these radiotracers to study the receptor density for patients including Alzheimer, Parkinson, Tourette syndrome, schizophrenia, and alcoholism and to evaluate the brain function of patients by SPECT or PET. 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, Dr. Daniel W. McPherson, Oak Ridge National Laboratory, and Neuromedica, Inc. We can summarize our research in the following : 1. We have developed a better method to produce a higher radiochemical yield of Br-76 radioisotope. 2. We have also developed a better radiobromination method for serotonin 5HT2A/5HT2C( DOB) and muscarinic (QNB) radioligands with a high radiolabelling yield. These radioligands could provide a high affinity and selectivity to serotonin and muscarinic receptors. These radioligands have been applied to monkey and rat for in vivo and autoradiography studies respectively. 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 radioligand was 50-70% when it was radiolabelled with Br-76 for 10 minutes at 45oC. 4. In 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 from I-123 to Br-76 for PET studies since PET imaging can provide a higher resolution and better imaging than SPECT. 5. [123I]-BZM radioligand was prepared to use to monitor the effect of a new drug, clozaprexin ( an analog of clozapine), in D-2 receptors in monkey brain in vivo by SPECT for Neuromedica, Inc . 6. We found that [I-123]-IQNB was a very useful radiotracer for the diagnostic of schizophrenia patients and was also useful for the monitoring of the drug therapy by SPECT. 7. In 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. 8. [I-123]-BZM and [I-123]-?CIT were prepared for patient studies by SPECT routinely.
| Heinz, A; Goldman, D; Jones, D W et al. (2000) Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 22:133-9 |
