RT Journal Article SR Electronic T1 A Visual Interpretation Algorithm for Assessing Brain Tauopathy with 18F-MK-6240 PET JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 444 OP 451 DO 10.2967/jnumed.122.264371 VO 64 IS 3 A1 John P. Seibyl A1 Jonathan M. DuBois A1 Annie Racine A1 Jessica Collins A1 Qi Guo A1 Dustin Wooten A1 Eddie Stage A1 David Cheng A1 Roger N. Gunn A1 Lilly Porat A1 Alex Whittington A1 Phillip H. Kuo A1 Masanori Ichise A1 Robert Comley A1 Laurent Martarello A1 Cristian Salinas YR 2023 UL http://jnm.snmjournals.org/content/64/3/444.abstract AB 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-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine (18F-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: 18F-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 18F-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.