Our main goal is to develop radioligands for dopamine, muscarinic acetylcholine, serotonin, serotonin/dopamine 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. These receptors are important because they play a main role for controlling the mental status for patients. Our interest is to apply these radioligands to study the receptor concentration for patients including Alzheimer, Parkinson, Tourette syndrome, schizophrenia, and alcoholism and to evaluate the patients? brain function 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, Dr. Fred Mishkin, UCLA Medical Center, and Neuromedica, Inc. We could summarize our research as follows: 1. We have improved the radiobromination method for dopamine, muscarinic acetylcholine (QNB and QNP), serotonin (DOB), and serotonin / dopamine transporters (?CIT) receptor radioligands to produce a higher radiochemical yield with Br-76 radioisotope. These radioligands provide a high affinity and selectivity to these receptors. Furthermore, these radioligands have been applied to autoradiography studies. 2. We have also developed a radiolabelling method for epidepride (D-2 receptor) with I-123. [I-123] epidepride provided a high affinity and selectivity to the D-2 receptors in vivo. The radiochemical yield for this radioligand was 50-80% when it was radiolabelled with I-123 for 5-10 minutes at room temperature. 3. 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 since the PET imaging can provide a high resolution and better imaging than SPECT. 4. [123I]-BZM radiligand 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. 5. Collaboration with Dr. Mishkin at UCLA Medical Center, we were able to use [I-123]-QNB as a radiotracer to study Alzheimer patients. [I-123]-QNB is a very useful radiotracer for the diagnostic of Alzheimer patients and was also useful for monitoring of the drug therapy by SPECT. 6. Collaboration with Dr. Zhang, we were able to study the estrogen effect on the receptor concentration of 5HT2A/C in the cortical region of the rat brain. Result indicated that estrogen could upregulate the serotonine, 5HT2A/C in the rat cortical region. 7. [I-123]-BZM and [I-123]-bCIT 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 |
