B Ravina, D Eidelberg, JE Ahlskog, RL Albin, DJ Brooks, M Carbon, V Dhawan, A Feigin, S Fahn, M Guttman, K Gwinn-Hardy, H McFarland, R Innis, RG Katz, K Kieburtz, SJ Kish, N Lange, JW Langston, K Marek, L Morin, C Moy, D Murphy, WH Oertel, G Oliver, Y Palesch, W Powers, J Seibyl, KD Sethi, CW Shults, P Sheehy, AJ Stoessl, R Holloway
Neurology 2005; 64 :208-215
Current evidence does not support the use of radiotracers for PD diagnosis or as a surrogate endpoint in clinical trials, according to this report from an NINDS-sponsored workshop on the role of neuroimaging in PD. The authors considered the published evidence for use of four radiotracer ligand imaging techniques.
– Fluorodopa PET. Because amino acid decarboxylase activity may be the rate-limiting step in dopamine synthesis, determination of fluorodopa uptake by F-dopa PET is thought to be a measure of AADC activity in surviving dopaminergic cells, rather than a direct measure of nigral cell count.
– DTBZ PET, which images the vesicular monoamine transporter 2 on the surface of dopamine-containing synaptic vesicles.
– beta-CIT SPECT, which images the dopamine transporter, responsible for recovering dopamine from the synaptic cleft.
– fluorodeoxyglucose PET, which measures changes in regional glucose metabolism.
The authors make the following comments:
– “These tracers measure biological processes that are related to the duration and severity of PD as measured by motor rating scales in the practically defined off state.
– “However, “these techniques do not assess the number or density of nigral dopaminergic neurons.
– “Predominantly nondopaminergic symptoms such as depression, cognitive impairment, and postural instability are major contributors to disability in PD, but may not be captured by dopamine-related tracers.
– ”While radiotracers can effectively distinguish between ET and PD, they cannot do so reliably for PD versus PSP, MSA, or other atypical parkinsonian syndromes.
– Regarding comparative trials of levodopa and dopamine agonists, “the interpretation of imaging data from these clinical trials is challenging because of the potential for direct pharmacologic regulation of the targets of these ligands.” Combined with conflicting imaging and clinical data from tissue transplant trials and the ELLDOPA study, “the clinical trials described here highlight the variable relationship between radiotracer imaging measures and clinical endpoints and show why no radiotracer imaging technique should be considered a surrogate endpoint in PD at this time.”