The PET/(F-18)-L-6-F-dopa imaging procedures of brain dopaminergic neurons, including a cyclotron producion of radioactive nuclide, radiochemical synthesis and purification of (F-18)-L-6-F-dopa, quality control of radiopharmacy, PET tomographic imaging, and the plasma metabolic profile of the imaging ligand has been developed and tested by the pre-clinical study. The results of the quality control of (F-18)-L-6-F-dopa revealed the chemical purity and the specific activity were greater than 95% and 350 mCi/mmol, respectively. This highly purified (F-18)-L-6-F-dopa preferentially imaged dopamine neurons in the brain in vivo and the imaging ratio of dopamine in the basal ganglia over that of background was improved from 1.5 to 3. Whereas, 2-F-dopa, a by- product of the fluorination procedure, produced no dopamine imaging. The results of the present study of PET/6-F-dopa imaging procedures for brain dopamine in conjunction with the MPTP-induced hemi-parkinsonian primate model have confirmed its potential clinical uses in determining degree of brain damage in parkinsonism and in measuring turnover rate of dopamine neurons in mental disorders. We have also developed a new SPECT imaging ligand, (I- 123)-labeled IBZM, for studying D2 dopamine receptors. The in vitro membrane binding study indicated that the binding of IBZM was highly selective to D2 dopamine receptors which was displaceable by both agonists and antagonists of the D2 dopamine receptor. The imaging of the D2 dopamine receptors in the A9, A10, and A16 dopaminergic systems were obtained in vivo within thirty minutes following the administration of the radioactively labeled IBZM by either SPECT or autoradiographic procedures. Thus, the results of this pre-clinical study have provided potential clinica1 brain imaging ligands for studying pre- and post-synaptic dopaminergic activities in patients with neuropschiatric or neurological disorders.
