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Correlation of in vivo positron emission tomography and in vitro autoradiography measurements using radiotracers for the dopamine system

University of British Columbia

Positron emission tomography (PET) is a noninvasive imaging technique that allows visualization of physiological function in living, conscious beings. In the field of Parkinson's disease (PD), PET is used in both basic and clinical research to provide insights into PD pathophysiology. Most importantly, it allows longitudinal analysis of disease progression and exploration of the compensatory neurochemical changes associated with long-term treatment or surgical intervention. Although the popularity of PET is increasing, the validation of many of the tracers in human use is lacking. Few studies have attempted to correlate the in vivo PET data with actual physiological processes. Elements of physiological processes are often measured in vitro by autoradiography (ARG) to eliminate confounding factors such as competition between the tracer and endogenous ligand. This study examines the relationship between PET and ARG measurements obtained with the same tracers, which target components of the dopamine system, in an MPTP non-human primate model of PD. Both presynaptic and postsynaptic tracers were examined in the same individuals representing a wide range of MPTP-induced clinical severity. PET and ARG measurements were also compared to behavioural assessment scores rating the severity of PD-like motor symptoms. PET binding potentials and ARG binding values obtained using the presynaptic tracers [ ¹¹C]DTBZ, [¹¹C]MP, and [³H]WIN 35,428 correlated significantly with each other and with behavioural assessments. In contrast, PET and ARG using the postsynaptic tracers raclopride and SCH-23390 labeled with either [¹¹C] or [³H] correlated weakly or not at all with each other and with behavioural scores. The results of this study suggest that both PET and ARG using presynaptic tracers provide comparable insights into disease pathophysiology and can evaluate clinical severity over a wide range of PD severity. They also raise awareness of the high individual variability in D1 and D2 dopamine receptor binding with progression of PD. These findings support the utility of PET using presynaptic tracers as a valuable brain imaging technique.

Text

2011-03-03

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http://hdl.handle.net/2429/31995

Experimental Medicine

University of British Columbia

Graduate