Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 57, Issue 4, Pages 574-581Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.115.158519
Keywords
positron emission tomography; kinetic modeling; parametric images; Alzheimer's disease; tau
Funding
- Swedish Research Council [05817]
- Swedish Brain Power
- Stockholm County Council
- Karolinska Institutet
- Uppsala County Council
- Uppsala University Hospital
- The Strategic Research Program in Neuroscience at Karolinska Institutet
- Foundation for Old Servants
- Gun and Bertil Stohne's Foundation
- KI foundations
- Swedish Brain Foundation
- Alzheimer Foundation in Sweden
- Swedish Foundation for Strategic Research
- EU FW7 large-scale integrating project INMiND
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Because a correlation between tau pathology and the clinical symptoms of Alzheimer disease (AD) has been hypothesized, there is increasing interest in developing PET tracers that bind specifically to tau protein. The aim of this study was to evaluate tracer kinetic models for quantitative analysis and generation of parametric images for the novel tau ligand (S)-F-18-THK5117. Methods: Nine subjects (5 with AD, 4 with mild cognitive impairment) received a 90-min dynamic (S)-F-18-THK5117 PET scan. Arterial blood was sampled for measurement of blood radioactivity and metabolite analysis. Volume-of-interest (VOI)-based analysis was performed using plasma-input models; single-tissue and 2-tissue (2TCM) compartment models and plasma-input Logan and reference tissue models; and simplified reference tissue model (SRTM), reference Logan, and SUV ratio (SUVr). Cerebellum gray matter was used as the reference region. Voxel-level analysis was performed using basis function implementations of SRTM, reference Logan, and SUVr. Regionally averaged voxel values were compared with VOI-based values from the optimal reference tissue model, and simulations were made to assess accuracy and precision. In addition to 90 min, initial 40- and 60-min data were analyzed. Results: Plasma-input Logan distribution volume ratio (DVR)-1 values agreed well with 2TCM DVR-1 values (R-2 = 0.99, slope = 0.96). SRTM binding potential (BPND) and reference Logan DVR-1 values were highly correlated with plasma-input Logan DVR-1 (R-2 = 1.00, slope approximate to 1.00) whereas SUVr(70-90)-1 values correlated less well and overestimated binding. Agreement between parametric methods and SRTM was best for reference Logan (R-2 = 0.99, slope = 1.03). SUVr(70-90)-1 values were almost 3 times higher than BPND values in white matter and 1.5 times higher in gray matter. Simulations showed poorer accuracy and precision for SUVr(70-90)-1 values than for the other reference methods. SRTM BPND and reference Logan DVR-1 values were not affected by a shorter scan duration of 60 min. Conclusion: SRTM BPND and reference Logan DVR-1 values were highly correlated with plasma-input Logan DVR-1 values. VOI-based data analyses indicated robust results for scan durations of 60 min. Reference Logan generated quantitative (S)-F-18-THK5117 DVR-1 parametric images with the greatest accuracy and precision and with a much lower white-matter signal than seen with SUVr(70-90)-1 images.
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