Invited Symposium: Assessing DA Function using PET Techniques
The ability to detect functional dopaminergic neurons in vivo is of considerable importance not only for the diagnosis of parkinsonism, but more importantly in order to assess the effects of interventions such as neural transplantation and potential neuroprotective therapies. There are currently three main approaches to imaging the presynaptic dopamine system: 6-[18F]6-fluoro-L-dopa (FD), which assesses the uptake and decarboxylation of FD to fluorodopamine (FDA) as well as the trapping of FDA within synaptic vesicles; labelling of the membrane dopamine transporter (DAT) with a variety of PET and SPECT agents and labelling of the central vesicular monoamine transporter (VMAT2). While each of these approaches provides somewhat similar information and should be expected to correlate roughly with the number of dopaminergic nerve terminals , important differences probably exist. Thus, while FD uptake has been shown to correlate with survival of nigral dopamine neurons in both animal and human forms of parkinsonism [1,2], this has not been demonstrated for the other tracers. VMAT2 binding is not selective for dopamine neurons, but labels other monoaminergic markers as well. However, in contrast to the DAT, VMAT2 activity is not thought to be subject to pharmacological regulation [3,4] and should therefore be an ideal marker of nerve terminal density. To date, there have been no studies directly comparing the utility of these various approaches to imaging dopamine neurons in patients with Parkinsonís disease (PD) and which assess whether disease progression and other factors affect them differently.
We have also been using PET to try and understand the basis for fluctuations in motor function and other complications of long-term therapy in PD. Possible factors include a loss of synaptic "buffering", reflecting reduced storage in nerve terminals, changes in the affinity or and/or density of dopamine receptors and changes downstream to dopamine receptors.
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|Stoessl, AJ; Lee, CS; Sossi, V; Calne, DB; Ruth, TJ; (1998). Imaging Studies of the Dopamine System in Parkinson's Disease. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/nahmiaspet/stoessl0717/index.html|
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