Feasibility of ¹⁸F-THK5351 PET quantitation using the Centiloid scale

Objectives: Tau PET imaging has played a key role in assessing tau pathology associated with Alzheimer disease (AD) in vivo. Standard methods of evaluation are important for PET data analysis, but such standards have not been established for tau PET imaging. The Centiloid (CL) scale has recently been proposed as a standard method of quantifying amyloid on PET images. We therefore aimed to determine whether CL values calculated from ¹⁸F-THK5351 PET images could serve as a standardized analytical method and identify target regions in direct comparisons of different tracers for tau PET.

Methods: We acquired ¹⁸F-THK5351 PET images 40 ± 5 minutes after tracer injection and MR images from 47 patients with normal cognition (NC) (age, 66 ± 8 years) and 28 with probable AD (age, 72 ± 8 years). All MRI data were co-registered and spatially normalized to the Montreal Neurological Institute (MNI)-152 template using PMOD software. All PET data were co-registered to the corresponding MRI data from each patient and spatially normalized into MNI-space by applying transformation parameters calculated from MRI images. The cerebellar cortex volume-of-interest (VOI) was manually designated as a reference region. Between-group comparisons proceeded using two-sample t-tests in Statistical Parametric Mapping version 12 (SPM12) for tau deposit values. The standard cortex (CTX) VOI was designated using t values to minimize the contribution of monoamine oxidase B (MAO-B) that non-specifically accumulates tau. Mean standardized uptake value ratios (SUVR) for tau for all patients were calculated using CTX-VOI and reference VOI. We converted SUVR to CL values.

Results: The parameters for two-sample t-tests comprised p < 0.01 (T = 2.40) and an extent threshold of 200. The retention of ¹⁸F-THK5351 was predominant in the angular gyrus, the inferior temporal cortex and parieto-occipital region in the patients with AD. The average SUVR ± standard deviation (SD) of patients with NC and AD were 1.35 ± 0.300 and 1.67 ± 0.180, respectively. The equation used to convert ¹⁸F-THK5351 to CL units was: CL = 100 (^TauSUVR - 1.35)/0.324. The CL values for patients with NC and AD ranged from -144 to 104 (0.290 ± 54.9) and -111 to 234 (105 ± 90.9), respectively.

Conclusions: Tau PET data with ¹⁸F-THK5351 can be expressed using the CL scale, and CL might serve as a standard quantitative method. The difference in ¹⁸F-THK5351 retention between NC and AD was larger when CL rather than SUVR was applied to tau PET images. The Centiloid scale can be applied to both amyloid PET and tau PET imaging.

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