Invited Symposium: Assessing DA Function using PET Techniques
Lee, CS (Neurodegenerative Disorders Centre, UBC & VH/HSC, Vancouver, Canada)
Sossi, V (Neurodegenerative Disorders Centre, UBC & VH/HSC, Vancouver, Canada)
Calne, DB (Neurodegenerative Disorders Centre, UBC & VH/HSC, Vancouver, Canada)
Ruth, TJ (UBC-TRIUMF PET Program, Vancouver, Canada)
The ability to image dopaminergic function in vivo may allow one to monitor the effects of various treatment interventions for PD, including potential neuroprotective agents and dopaminergic cell transplants. At the UBC-TRIUMF program, we have used positron emission tomography (PET) to study the uptake and distribution of 3 presynaptic markers of the nigrostriatal dopamine (DA) system: [18F]6-fluoro-L-dopa (FD; uptake and decarboxylation of DOPA), [11C]-d-threo-methylphenidate (MP; membrane DA transporter [DAT]) and [11C](±)dihydrotetrabenazine (DTBZ; central vesicular monoamine transporter [VMAT2]). It appears that these 3 markers all provide similar but different information; thus, as VMAT2 is not subject to regulation by DA, it is felt to provide a better estimate of nerve terminal density. In contrast, although we have shown that FD uptake correlates with nigral cell counts post-mortem, it is relatively increased compared to DTBZ binding. This suggests that decarboxylation of FD may be upregulated in early PD as a compenstory mechanism; this is further supported by our recent observation that in some patients FD uptake is markedly reduced on treatment with the DA receptor agonist bromocriptine. MP binding is in contrast reduced compared to DTBZ binding; this suggests that the DAT is downregulated, in an effort to maximize the availability of synaptic DA. Prolonged FD studies are being used to estimate the loss of FDA and the rate of DA turnover. We are also studying post-synaptic DA receptors with [11C]SCH 23390 (D1 receptor) and [11C]raclopride (RAC; D2 receptor). D2 binding is increased in early, untreated PD, but there is no apparent relationship between complications of treatment, including fluctuations and dyskinesias, and either D1 or D2 binding. However, the ability of endogenous DA to compete for RAC binding can be used to estimate the time course of DA release following levodopa treatment; we can also assess the ability of novel agonists to displace RAC binding.
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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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