TY - JOUR T1 - Relationship between the accumulation of THK-5351 and PiB in each cerebral region from cognitively normal to Alzheimer type dementia, a PET study JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1464 LP - 1464 VL - 60 IS - supplement 1 AU - Akinori Takenaka AU - Kaori Iwata AU - Takashi Kato AU - Yasuyuki Kimura AU - Yutaka Arahata AU - Akinori Takeda AU - Masahiko Bundo AU - Kengo Ito AU - Akinori Nakamura Y1 - 2019/05/01 UR - http://jnm.snmjournals.org/content/60/supplement_1/1464.abstract N2 - 1464Introduction: THK-5351 (THK) was developed as a PET ligand for tau imaging. However, it is necessary to reevaluate the usefulness in pathophysiological researches since off-target binding of THK to monoamine oxidase B (MAO-B) was revealed. In Alzheimer's disease (AD), amyloid is thought to trigger the neocortical tau deposition that causes neurodegeneration accompanied by astroglyosis. As the activity of MAO-B is known to increase in relation to astroglyosis, accumulation of THK is expected to reflect tau pathology and/or neurodegeneration following amyloid deposition in AD progression. In this study we examined whether the accumulation of THK and PiB are related to each other in each cerebral region in the AD continuum from cognitively normal (CN) to Alzheimer type dementia (ADD). Methods: Subjetcs were 40 CN with PiB negative scans (CNn), 11 CN with PiB positive scans (CNp), and 17 patients with ADD or mild cognitive impairment (MCI) with PiB positive scans, with a total of 68 individuals (74.6 ± 5.2 year old), who underwent PiB and THK PET scans by the PET-CT camera, Biograph 16 TruePoint (Siemens, Germany). 3D-emission scans of PiB PET were performed from 50 to 70 min after intravenous injection of 555+/-185 MBq PiB. 3D-emission scans of THK PET were carried out from 40 to 60 min after intravenous injection of 185+/-37 MBq THK. 3D T1-weighted MR images were obtained using 3T MAGNETOM Trio scanner (Siemens, Germany). THK-SUVR and PiB-SUVR PET images were spatially normalized using the coregistrated 3D-T1 MR images to calculate SUVR values in each region of interest (ROI) using the automatic anatomical labeling (AAL) atlas. PiB and THK SUVR images were generated by dividing the PiB and THK images by the averaged ROI values in each of the cerebellar hemispheres on a pixel-by-pixel basis. PiB PET images were visually read by two experienced nuclear medicine physicians who were blind to the clinical data to evaluate whether PiB PET images were positive or negative scans. Partial correlation coefficients between THK-SUVR and PiB-SUVR values adjusting for age were calculated for each ROI value. ROI based statistical analyses were performed using SPSS ver. 21 (IBM, New York, USA). THK-SUVR images were analyzed by multiple regression analyses on pixel by pixel basis with covariates of age and the PiB-SUVR values of each ROI using SPM8. Results: THK-SUVR value was higher than PiB-SUVR value in the hippocampus, while no evident difference was observed in the neocortical areas. In all the participants, there was a significant correlation between the PiB-SUVR value and THK-SUVR value in many cerebral regions (r =0.36, p =0.003). In particular, strong links were observed between the regional accumulation of PiB and THK in the left inferior temporal lobe and the occipital lobe (r > 0.5, p < 0.001). In partial correlation coefficient of PiB and THK, no significant correlation nor constant tendency were observed in all the regions in CNp. However, significant correlations were observed in the inferior temporal lobe, the inferior parietal lobules, and the occipital lobe in the patient group (AD, MCI) (r > 0.5, p < 0.05). In a SPM analysis, mean cortical SUVR value of PiB was positively associated with SUVR values of THK in the temporo-parietal association area, frontal association area, posterior cingulate, and precuneus. ROI values of PiB SUVR in the inferior temporal and occipital cortices showed positive association with THK SUVR values mainly in the inferior temporal and occipital cortices, respectively (FEW p< 0.05). Conclusion: The results suggest that the accumulation of THK-5351 in the neocortical area reflects pathological changes of AD following amyloid deposition in the symptomatic stages such as MCI and ADD. ER -