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Parkinson's Disease: Parkinson's is a neurodegenerative disorder resulting from the progressive death of dopaminergic neurons in the nigrostriatal pathway (pars compacta of the substantia nigra and locus ceruleus, and presynaptic dopaminergic nerve terminals in the caudate nucleus and putamen) [8,12]. Symptoms consist of rigidity, bradykinesia, difficulty in initiating and stopping movement, and a resting tremor [8]. Motor disturbances begin only after a loss of approximately 70-80% of striatal dopamine- thus, there is a long latent period which precedes the development of clinical symptoms [12]. Approximately 10% of patients with Parkinson's develop a dementia [8] and biparietal hypometabolism identical to Alzheimer's is seen in these patients (this finding is typically not found in Parkinson's patients without dementia) [8]. The loss of dopaminergic nerve terminals in the basal ganglia can be detected by PET imaging with 6-[18F] fluoro-DOPA (an analog of the dopamine precursor dihydroxyphenylalanine [DOPA]) to study the presynaptic component of the nigrostriatal dopamine system and dopamine metabolism. 6-FD is largely metabolized peripherally by DOPA decarboxylase (DDC) to F-18 fluorodopamine before penetrating the BBB. This factor, as well as other peripheral metabolites which may cross the BBB, complicate the brain uptake of 6-FD. Inhibitors of DDC, such as Carbidopa, when injected before administration of the 6-FD improve brain uptake of the tracer considerably [Seminars, Oct. 94, p.339]. The cerebral radioactivity measured after the administration of 6-FD is a function of uptake of the isotope into the brain and its subsequent metabolism to dopamine. In Parkinson's disease, the decrease in 6-FD accumulation is much more severe in the putamen than in the caudate nucleus [Seminars, Oct. 94, p.339]. F-18 labeled derivatives of m-tyrosine have also been used to study Parkinson's disease. m-Tyrosine is a substrate for the enzyme aromatic amino acid decarboxylase which is responsible for the conversion of DOPA to dopamine. Marked reduction in activity within the basal ganglia (putamen and caudate) is seen in patients with Parkinson's disease with both 6-FD and m-tyrosine. PET studies of alterations in D2 dopamine receptors have been conflicting. Patients that have been studied with C-11 N-methylspiperone while maintained on their usual dose of L-DOPA display essentially normal levels of dopamine receptors, despite the fact that F-18 fluoro-DOPA uptake is markedly reduced. C-11 Nomifensine has been developed to study the dopamine reuptake system located on the presynaptic nerve terminals. This agent also demonstrates decreased uptake within the basal ganglia of Parkinson's patients. Thomas Berdine --- Outgoing mail is certified Virus Free. Checked by AVG anti-virus system (http://www.grisoft.com). Version: 6.0.434 / Virus Database: 243 - Release Date: 12/25/2002 ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn