PT - JOURNAL ARTICLE AU - Cécile Tissot AU - Stijn Servaes AU - Firoza Z. Lussier AU - João Pedro Ferrari-Souza AU - Joseph Therriault AU - Pâmela C. L. Ferreira AU - Gleb Bezgin AU - Bruna Bellaver AU - Douglas Teixeira Leffa AU - Sulantha S. Mathotaarachchi AU - Mira Chamoun AU - Jenna Stevenson AU - Nesrine Rahmouni AU - Min Su Kang AU - Vanessa Pallen AU - Nina Margherita Poltronetti AU - Yi-Ting Wang AU - Jaime Fernandez-Arias AU - Andrea L. Benedet AU - Eduardo R. Zimmer AU - Jean-Paul Soucy AU - Dana L. Tudorascu AU - Ann D. Cohen AU - Madeleine Sharp AU - Serge Gauthier AU - Gassan Massarweh AU - Brian J. Lopresti AU - William E. Klunk AU - Suzanne L. Baker AU - Victor L. Villemagne AU - Pedro Rosa-Neto AU - Tharick A. Pascoal TI - The association of age-related and off-target retention with longitudinal quantification of [<sup>18</sup>F]MK6240 tau-PET in target regions. AID - 10.2967/jnumed.122.264434 DP - 2022 Nov 01 TA - Journal of Nuclear Medicine PG - jnumed.122.264434 4099 - http://jnm.snmjournals.org/content/early/2022/11/17/jnumed.122.264434.short 4100 - http://jnm.snmjournals.org/content/early/2022/11/17/jnumed.122.264434.full AB - [18F]MK6240 tau-PET tracer quantifies brain tau neurofibrillary tangles (NFT) load in Alzheimer’s disease (AD). The aims of our study are to test the stability of common reference region estimates in the cerebellum over time and across diagnoses and evaluate the effects of age-related and off-target retention on the longitudinal quantification of [18F]MK6240 in target regions. Methods: We assessed reference, target, age-related and off-target regions in 125 individuals across the aging and AD spectrum with longitudinal [18F]MK6240 standardized uptake values (SUV) and ratios (SUVR) (2.25±0.40 years of follow-up duration). We obtained SUVR from meninges, exhibiting frequent off-target retention with [18F]MK6240. Additionally, we compared tracer uptake between 37 cognitively unimpaired (CU) young (CUY, mean age: 23.41±3.33 years) and 27 CU older adults (CU, amyloid-β and tau negative, mean age: 58.50±9.01 years) to identify possible, non-visually apparent, age-related signal. Two-tailed t-test and Pearson correlations tested the difference between groups and associations between changes in region uptake, respectively. Results: Inferior cerebellar grey (CG) SUV did not differ based on diagnosis and Aβ status, cross-sectionally and over time. [18F]MK6240 uptake was significantly different between CUY and CU older adults in putamen/pallidum (affecting ~75% of the region) and in Braak II region (affecting ~35%). Changes in meningeal and putamen/pallidum SUVRs were not significantly different from zero, nor varied across diagnostic groups. We did not observe significant correlations between longitudinal changes in age-related or meningeal off-target retention and changes in target regions, whereas changes in all target regions were highly correlated. Conclusion: Inferior CG was similar across diagnostic groups cross-sectionally and stable over time, thus deemed a suitable reference region for quantification. Despite not being visually perceptible, [18F]MK6240 has age-related retention in subcortical regions, in much lower magnitude but topographically co-localized with significant off-target signal of the first-generation tau tracers. The lack of correlation between changes in age-related/meningeal and target retention suggests little influence of possible off-target signals on longitudinal tracer quantification. Nevertheless, the age-related retention in Braak II needs to be further investigated. Future post-mortem studies should elucidate the source of the newly reported age-related [18F]MK6240 signal, and in vivo studies further explore its impact on tracer quantification.