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. William C Eckelman, NIH, Dr. Richard Glennon, University of Virginia, and school of medicine, Dr. Lei Zhang, NIMH, Dr. Robert Innis, NIMH, Dr. He Li, Naval Medical Center, and Dr. Fred Mishkin, UCLA Medical Center. Our research can be summarized as follows: 1. To improve the radioiodination method for serotonin / dopamine transporters (?CIT) receptor radioligands. The radioiodination yield was improve from 70% to >90% . 2. To develop a radiolabelling method for epidepride (D-2 receptor) with Br-76. [Br-76]Bromoepidepride provides a high affinity and selectivity to the D-2 receptors in vivo. The radiochemical yield for this radioligand was >60% in the presence of acetic acid and hydrogen peroxide when it was radiolabelled with Br-76 for 10 minutes at 65 degrees Celsius. 3. Collaboration with Dr. Eckelman from the PET imaging group, we were able to prepare Br-76, positron emitter with a half-life 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. The radiobromination has been applied to radioligands such as [Br-76]Bromoepidepride, [Br-76] BrQNB, and [Br-76] Brsigma. 4. Collaboration with Dr. Mishkin at UCLA Medical Center, we were able to use [I-123]IQNB as a radiotracer to study the response to acetylcholinesterase inhibitors in dementia secondary to Alzheimer's Disease, vascular dementia, and mixed dementia. 5. Collaboration with Dr. Zhang, we were able to study the estrogen effect on the receptor concentration of sigma and muscarinic receptor density in the rat brain. Result indicated that estrogen could upregulate sigma and muscarinic receptor density in the brain region. 6. Collaboration with Dr. Li at the Naval Medical Center, we were able to study the change of receptor density concentration under the normal control, acute, and chronic stress. The serotonine, 5HT2A/C of [I-123]IDOB has been applied for the studies. 7. [I-123]-BZM and [I-123]-?CIT were prepared for schizophrenia patient studies by SPECT routinely. 8. To develop radioiodination method for 5IA, a nicotinic receptor, in the collaboration effort with Dr. Robert Innis. The radiochemical yield for this radioligand was >80% in the presence of HCl and peracetic acid with I-123 for 10 minutes at 65 degrees Celsius. The information will be used for the IND application.
| Heinz, A; Goldman, D; Jones, D W et al. (2000) Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 22:133-9 |
