RT Journal Article
SR Electronic
T1 [<sup>18</sup>F]MK-6240 Radioligand Delivery Indices as Surrogates of Cerebral Perfusion: Bias and Correlation Against [<sup>15</sup>O]Water
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP jnumed.124.268701
DO 10.2967/jnumed.124.268701
A1 Fu, Jessie Fanglu
A1 Juttukonda, Meher R.
A1 Garimella, Arun
A1 Salvatore, Andrew N.
A1 Lois, Cristina
A1 Ranasinghe, Anthony
A1 Efthimiou, Nikos
A1 Sari, Hasan
A1 Aye, William
A1 Guehl, Nicolas J.
A1 El Fakhri, Georges
A1 Johnson, Keith A.
A1 Dickerson, Bradford C.
A1 Izquierdo-Garcia, David
A1 Catana, Ciprian
A1 Price, Julie C.
YR 2025
UL http://jnm.snmjournals.org/content/early/2025/02/13/jnumed.124.268701.abstract
AB [18F]MK-6240 PET (where MK-6240 is 6-(fluoro)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine) is used to assess in vivo tau deposition across the Alzheimer disease (AD) spectrum. We aimed to quantify the associations and bias of early-frame [18F]MK-6240 PET as surrogates for cerebral perfusion against gold standard [15O]water PET and the potential impact of cerebral perfusion on [18F]MK-6240 tau quantification across aging and the AD spectrum. Methods: Fourteen cognitively normal (CN, 4 young CN and 10 old CN) and 3 AD participants underwent dynamic [18F]MK-6240 PET, with 9 undergoing arterial sampling. A subset (n = 11) underwent [15O]water PET. [18F]MK-6240 perfusion indices were estimated as radiotracer delivery indices K1 (using 2-tissue-compartment models), and relative perfusion indices were estimated as R1 (using compartmental and reference tissue models, cerebellar gray matter reference region) and early-frame SUV ratio (0–3 min). [15O]water K1 and R1 were estimated using 1-tissue-compartment models). [18F]MK-6240 tau burden was estimated using distribution volume ratio and SUV ratio at 90–110 min. Spearman correlations, linear mixed-effect models, and Bland–Altman analyses examined relationships between [18F]MK-6240 perfusion indices against [15O]water and between estimates of perfusion and tau burden in tau-relevant regions. The impact of partial-volume correction was examined. Results: Significant correlations were observed between [18F]MK-6240 K1 and [15O]water K1 (ρ = 0.57); However, [18F]MK-6240 K1 underestimated [15O]water K1 by up to 50%, with a strong negative proportional bias. Significant correlations were observed between [18F]MK-6240 relative perfusion and [15O]water R1 (ρ &gt; 0.84), with minimal bias. In 2 AD participants, significant correlations were observed between perfusion and [18F]MK-6240 retention. Applying partial-volume correction did not significantly impact the correlations or improve the underestimations in [18F]MK-6240 K1. Conclusion: Using head-to-head [18F]MK-6240 and [15O]water data, we showed that [18F]MK-6240 exhibited a relatively low extraction fraction, leading to underestimation of cerebral perfusion. Our results provide further support for [18F]MK-6240 R1 as a reliable estimate of relative cerebral perfusion, with strong associations and minimal bias compared with [15O]water. In addition, lower perfusion may be associated with higher [18F]MK-6240 retention in tau-relevant regions in AD. These findings further support the use of dynamic [18F]MK-6240 in dual-imaging assessments of tau burden and vascular health.