Invited Symposium: Assessing DA Function using PET Techniques



Materials & Methods


Discussion & Conclusion



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Imaging Studies of the Dopamine System in Parkinson's Disease

Contact Person: A. Jon Stoessl (jstoessl@interchange.ubc.ca)

Discussion and Conclusion

Although (as expected), markers for FD uptake, DAT binding and VMAT2 binding all displayed a similar pattern, with an anteroposterior gradient of reduced activity, closer examination of the data reveal subtle differences. Thus, compared to DTBZ binding (which should in theory give the best estimate of nerve terminal density), FD uptake was relatively preserved, suggesting compensatory upregulation of decarboxylase activity. This is partially supported by the observation that at least in some patients, bromocriptine therapy results in a reduction of FD Ki, in keeping with downregulation of decarboxylase, as has been demonstrated in a number of in vitro studies [10,11], as well as in vivo studies in the rat [12]. The latter observation has a more immediate and practical implication, in that FD PET is often regarded as the "gold standard" for assessing viability of fetal dopaminergic grafts, as well as the effects of neuroprotective therapy. The possibility that dopamine agonists may affect the measurements must be borne in mind when interpreting the results of such interventions.

The lack of a significant difference in FD Ki between stable PD patients and those with motor fluctuations suggests that a lack of "synaptic buffering" is unlikely to be the major factor underlying such fluctuations. Loss of buffering capacity might occur as a consequence of loss of nerve terminals, but there does not seem to be a difference between the two patient groups. Previous investigators [13] have reported differences in FD uptake between stable and fluctuating patients, measured over 4 hours following tracer administration. Activity determined over longer scan times may reflect the egress of FDA from nerve terminals and its enzymatic conversion to labelled metabolites. Thus, the results of Leenders et al. may actually reflect an increase in dopamine turnover (i.e. in the ratio kloss/Ki)[14, 15]. We are currently in the process of assessing this possibility, by performing prolonged FD scans. The studies of endogenous dopamine release (Fig. 4) may also shed further light on this.

To date, there has been little evidence that complications of PD are associated with changes in the binding potential of either D1 or D2 receptors, in keeping with similar results reported by Turjanski and colleagues [16]. The possibility of altered affinity states is currently being tested, but we are cognizant of the likelihood that complications may result from changes downstream to dopamine receptors and will not be detected by these studies. In the future, the ability to image cellular signalling machinery may help resolve these important questions.

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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
© 1998 Author(s) Hold Copyright