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In vivo characterization of pathologic deposition of tau protein in the human brain by PET imaging is a promising tool in drug development trials of Alzheimer disease (AD). 6-(fluoro- 18 F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ( 18 F-MK-6240) is a radiotracer with high selectivity and subnanomolar affinity for neurofibrillary tangles that shows favorable nonspecific brain penetration and excellent kinetic properties. The purpose of the present investigation was to develop a visual assessment method that provides both an overall assessment of brain tauopathy and regional characterization of abnormal tau deposition. Methods: 18 F-MK-6240 scans from 102 participants (including cognitively normal volunteers and patients with AD or other neurodegenerative disorders) were reviewed by an expert nuclear medicine physician masked to each participant's diagnosis to identify common patterns of brain uptake. This initial visual read method was field-tested in a separate, nonoverlapping cohort of 102 participants, with 2 additional naïve readers trained on the method. Visual read outcomes were compared with semiquantitative assessments using volume-of-interest SUV ratio. Results: For the visual read, the readers assessed 8 gray-matter regions per hemisphere as negative (no abnormal uptake) or positive (1%-25% of the region involved, 25%-75% involvement, or >75% involvement) and then characterized the tau binding pattern as positive or negative for evidence of tau and, if positive, whether brain uptake was in an AD pattern. The readers demonstrated agreement 94% of the time for overall positivity or negativity. Concordance on the determination of regional binary outcomes (negative or positive) showed agreement of 74.3% and a Fleiss κ of 0.912. Using clinical diagnosis as the ground truth, the readers demonstrated a sensitivity of 73%-79% and specificity of 91%-93%, with a combined reader-concordance sensitivity of 80% and specificity of 93%. The average SUV ratio in cortical regions showed a robust correlation with visually derived ratings of regional involvement ( r = 0.73, P < 0.0001). Conclusion: We developed a visual read algorithm for 18 F-MK-6240 PET offering determination of both scan positivity and the regional degree of cortical involvement. These cross-sectional results show strong interreader concordance on both binary and regional assessments of tau deposition, as well as good sensitivity and excellent specificity supporting use as a tool for clinical trials., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Recently, Amyloid IQ was introduced as a new canonical image-based algorithm to quantify amyloid PET scans and demonstrated increased power over traditional SUV ratio (SUVR) approaches when assessed in cross-sectional and longitudinal analyses. We build further on this mathematical framework to develop a Tau IQ algorithm for the quantitative analysis of the more complex spatial distribution displayed by tau PET radiotracers. Methods: Cross-sectional ( n = 615) and longitudinal ( n = 149) 18 F-flortaucipir data were obtained from the Alzheimer's Disease Neuroimaging Initiative along with necessary adjunct amyloid PET and T1-weighted structural MRI data. A subset of these data were used to derive a chronological tau dataset, using Amyloid IQ analysis of associated amyloid PET data to calculate the subject's temporal position in the canonical AD disease process, from which canonical images for the nonspecific and specific binding components of 18 F-flortaucipir in AD were calculated. These 2 canonical images were incorporated into the Tau IQ algorithm that enables the quantification of both global and local tau outcome measures using an image-based regression and statistical parametric analysis of the initial residual image. Performance of the Tau IQ algorithm was compared with SUVR approaches for cross-sectional analyses, longitudinal analyses, and correlation with clinical measures (Alzheimer Disease Assessment Scale-Cognitive Subscale [ADAS-Cog], Clinical Dementia Rating scale-sum of boxes [CDR-SB], and Mini-Mental State Examination [MMSE]). Results: Tau IQ successfully calculated global tau load (Tau L ) in all 791 scans analyzed (range, -3.5% to 185.2%; mean ± SD, 23% ± 20.5%) with a nonzero additional local tau component being required in 31% of all scans (cognitively normal [CN], 22%; mild cognitive impairment [MCI], 35%; dementia, 72%). Tau IQ was compared with the best SUVR approach in the cross-sectional analysis (Tau L increase in effect size: CN- vs. CN+, +45%; CN- vs. MCI+, -5.6%; CN- vs. dementia+, +2.3%) (+/- indicates amyloid-positive or -negative) and correlation with clinical scores (Tau L increase in r 2 : CDR-SB+, 7%; MMSE+, 38%; ADAS-Cog+, 0%). Tau IQ substantially outperformed SUVR approaches in the longitudinal analysis (Tau IQ increase in power: CN+, >3.2-fold; MCI+, >2.2-fold; dementia+, >2.9-fold). Conclusion: Tau L as calculated by Tau IQ provides a superior approach for the quantification of tau PET data. In particular, it provides a substantial improvement in power for longitudinal analyses and the early detection of tau deposition and thus should have significant value for clinical imaging trials in AD that are investigating the attenuation of tau deposition with novel therapies., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

PET with 18 F-FDG has been increasingly applied, predominantly in the research setting, to study drug effects and pulmonary biology and to monitor disease progression and treatment outcomes in lung diseases that interfere with gas exchange through alterations of the pulmonary parenchyma, airways, or vasculature. To date, however, there are no widely accepted standard acquisition protocols or imaging data analysis methods for pulmonary 18 F-FDG PET/CT in these diseases, resulting in disparate approaches. Hence, comparison of data across the literature is challenging. To help harmonize the acquisition and analysis and promote reproducibility, we collated details of acquisition protocols and analysis methods from 7 PET centers. From this information and our discussions, we reached the consensus recommendations given here on patient preparation, choice of dynamic versus static imaging, image reconstruction, and image analysis reporting., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Mitochondrial complex 1 is involved in maintaining brain bioenergetics; σ-1 receptor responds to neuronal stress; and synaptic vesicle protein 2A reflects synaptic integrity. Expression of each of these proteins is altered in neurodegenerative diseases. Here, we characterize the kinetic behavior of 3 PET radioligands- 18 F-BCPP-EF, 11 C-SA-4503, and 11 C-UCB-J-for the measurement of mitochondrial complex 1, σ-1 receptor, and synaptic vesicle protein 2A, respectively, and determine appropriate analysis workflows for their application in future studies of the in vivo molecular pathology of these diseases. Methods: Twelve human subjects underwent dynamic PET scans with each radioligand, including associated arterial blood sampling. A range of kinetic models was investigated to identify an optimal kinetic analysis method for each radioligand and a suitable acquisition duration. Results: All 3 radioligands readily entered the brain and yielded heterogeneous uptake consistent with the known distribution of the targets. The optimal models determined for the regional estimates of volume of distribution were multilinear analysis 1 (MA1) and the 2-tissue-compartment model for 18 F-BCPP-EF, MA1 for 11 C-SA-4503, and both MA1 and the 1-tissue-compartment model for 11 C-UCB-J. Acquisition times of 70, 80, and 60 min for 18 F-BCPP-EF, 11 C-SA-4503, 11 C-UCB-J, respectively, provided good estimates of regional volume of distribution values. An effect of age was observed on 18 F-BCPP-EF and 11 C-UCB-J signal in the caudate. Conclusion: These ligands can be assessed for their potential to stratify patients or monitor the progression of molecular neuropathology in neurodegenerative diseases., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)