Comparison of Early-Phase C-11-Deuterium-L-Deprenyl and C-11-Pittsburgh Compound B PET for Assessing Brain Perfusion in Alzheimer Disease
2016 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 57, no 7, 1071-1077 p.Article in journal (Refereed) PublishedText
The PET tracer C-11-deuterium-L-deprenyl (C-11-DED) has been used to visualize activated astrocytes in vivo in patients with Alzheimer disease (AD). In this multitracer PET study, early-phase C-11-DED and C-11-Pittsburgh compound B (C-11-PiB) (eDED and ePiB, respectively) were compared as surrogate markers of brain perfusion, and the extent to which C-11-DED binding is influenced by brain perfusion was investigated. METHODS: C-11-DED, C-11-PiB, and F-18-FDG dynamic PET scans were obtained in age-matched groups comprising AD patients (n = 8), patients with mild cognitive impairment (n = 17), and healthy controls (n = 16). A modified reference Patlak model was used to quantify C-11-DED binding. A simplified reference tissue model was applied to both C-11-DED and C-11-PiB to measure brain perfusion relative to the cerebellar gray matter (R-1) and binding potentials. C-11-PiB retention and F-18-FDG uptake were also quantified as target-to-pons SUV ratios in 12 regions of interest (ROIs). RESULTS: The strongest within-subject correlations with the corresponding R-1 values (R-1,R-DED and R-1,R-PiB, respectively) and with F-18-FDG uptake were obtained when the eDED and ePiB PET data were measured 1-4 min after injection. The optimum eDED/ePiB intervals also showed strong, significant ROI-based intersubject Pearson correlations with R-1,R-DED/R-1,R-PiB and with F-18-FDG uptake, whereas C-11-DED binding was largely independent of brain perfusion, as measured by eDED. Corresponding voxelwise correlations confirmed the ROI-based results. Temporoparietal eDED or ePiB brain perfusion measurements were highly discriminative between patient and control groups, with discriminative ability statistically comparable to that of temporoparietal F-18-FDG glucose metabolism. Hypometabolism extended over wider regions than hypoperfusion in patient groups compared with controls. CONCLUSION: The 1- to 4-min early-frame intervals of C-11-DED or C-11-PiB are suitable surrogate measures for brain perfusion. C-11-DED binding is independent of brain perfusion, and thus C-11-DED PET can provide information on both functional (brain perfusion) and pathologic (astrocytosis) aspects from a single PET scan. In comparison with glucose metabolism, early-phase C-11-DED and C-11-PiB perfusion appear to provide complementary rather than redundant information.
Place, publisher, year, edition, pages
2016. Vol. 57, no 7, 1071-1077 p.
amyloid, astrocytosis, brain perfusion, early-phase PET
Radiology, Nuclear Medicine and Medical Imaging
IdentifiersURN: urn:nbn:se:uu:diva-300056DOI: 10.2967/jnumed.115.168732ISI: 000378979200016PubMedID: 26912447OAI: oai:DiVA.org:uu-300056DiVA: diva2:950765
FunderSwedish Research Council, 05817Swedish Foundation for Strategic Research Knut and Alice Wallenberg FoundationThe Karolinska Institutet's Research FoundationThe Swedish Brain FoundationThe Dementia Association - The National Association for the Rights of the DementedEU, FP7, Seventh Framework ProgrammeStiftelsen Gamla TjänarinnorWenner-Gren Foundations