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¹¹C-DTBZ and ¹⁸F-FDG PET Measures in Differentiating Dementias

¹ Division of Nuclear Medicine, Department of Radiology, University of Michigan School of Medicine, Ann Arbor, Michigan
² Department of Neurology, University of Michigan School of Medicine, Ann Arbor, Michigan
³ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan
⁴ Geriatrics Research, Education and Clinical Center, Ann Arbor Veterans Administration Medical Center, Ann Arbor, Michigan

Accurate, early differentiation of dementias will become increasingly important as new therapies are introduced. Differential diagnosis by standard clinical criteria has limited accuracy. PET offers the potential to increase diagnostic accuracy. ¹⁸F-FDG studies detect metabolic abnormalities in demented patients, but with limited specificity. PET also offers the ability to quantify other biochemical markers that can yield additional useful diagnostic information. We demonstrate that (+)-¹¹C-dihydrotetrabenazine (¹¹C-DTBZ) studies, which provide an index of nigrostriatal terminal density (distribution volume; DV), also provide a measure of transport (K₁) that produces information comparable to the metabolic measure of ¹⁸F-FDG. Methods: Fifty-two patients and 19 control subjects underwent both ¹¹C-DTBZ and ¹⁸F-FDG PET scans. Seven had the clinical diagnosis of frontotemporal dementia (FTD), 25 had Alzheimer’s disease (AD), and 20 had dementia with Lewy bodies (DLB). DTBZ scans provided maps of K₁ and DV, whereas ¹⁸F-FDG scans provided maps of glucose metabolism. Correlation analyses were performed between the different PET measures both within and across subjects. Discriminant analysis using logistic regression compared the performance of ¹¹C-DTBZ K₁ and ¹⁸F-FDG in differentiating subject groups. Three experienced PET researchers participated in an interrater reliability study using both ¹¹C-DTBZ K₁ and ¹⁸F-FDG images. Results: Within-subject correspondence between ¹¹C-DTBZ K₁ and ¹⁸F-FDG measures was high, with correlations averaging 0.92. Correlations between the ¹¹C-DTBZ DV and either K₁ or ¹⁸F-FDG were far lower, averaging 0.37 and 0.31, respectively, indicating the much higher degree of similarity in information provided by K₁ and ¹⁸F-FDG compared with the very different information provided by ¹¹C-DTBZ DV. Discriminant analysis demonstrated that ¹¹C-DTBZ K₁ and ¹⁸F-FDG yielded similar levels of sensitivity and specificity for differentiating the subjects in this study. Including ¹¹C-DTBZ DV in addition to either K₁ or ¹⁸F-FDG improved discrimination between groups. The raters classified PET scans nearly equivalently using K₁ and ¹⁸F-FDG. Conclusion: Multiple PET measures, whether 2 parameters from a single PET study such as ¹¹C-DTBZ K₁ and DV, or 2 parameters from different studies such as ¹⁸F-FDG and ¹¹C-DTBZ DV, offer complementary information useful for diagnosing dementias. K₁ and DV images generated from a single ¹¹C-DTBZ scan provide as much diagnostic information as 2-scan studies using both ¹¹C-DTBZ and ¹⁸F-FDG.

Key Words: PET • dementia • nigrostriatal terminals • (+)-¹¹C-dihydrotetrabenazine • ¹⁸F-FDG

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