Author: Brecca Bettcher, Tobey J Betthauser, Bradley T Christian, Sterling Johnson, Lisette LeMerise, Max McLachlan, Andrew McVea, Dhanabalan Murali, Ali Pirasteh, Matthew Zammit 👨🔬
Affiliation: University of Wisconsin-Madison School of Medicine and Public Health and Waisman Center 🌍
Purpose: The radiotracer [18F]NAV4694 is a desirable alternative to [11C]PiB for measuring amyloid neuropathology related to Alzheimer’s disease (AD), possessing similar imaging characteristics and favorable distribution logistics. Longitudinal amyloid studies must account for the variability of outcome measures when transitioning to an alternative radiotracer. While the Centiloid (CL) scale has proven reliable in quantifying PET β-amyloid measures cross-sectionally, this work examines how transitioning from [11C]PiB to [18F]NAV4694 impacts individuals’ amyloid trajectory as measured by Centiloids.
Methods: 32 participants with ≥1 [11C]PiB scans, followed by a [18F]NAV4694 scan, were examined from ongoing AD studies at the University of Wisconsin (Table 1). PET images were realigned, summed 50-70min, coregistered to associated T1w MRIs, normalized to MNI space, and smoothed by 6mm. Cortical SUVR and CL were calculated using a whole cerebellum reference region. Rate of amyloid accumulation (CL/year) in amyloid positive individuals was compared to published values. Longitudinal analyses were performed for participants with at least two PiB scans, allowing for direct comparison of PiB-to-PiB changes and PiB-to-NAV changes. An amyloid negative (A-) subset was defined as participants who remained firmly amyloid negative (CL < 10) across all observations.
Results: Within-participant [11C]PiB and [18F]NAV4694 images were virtually indistinguishable by visual inspection. The average rate of amyloid accumulation in amyloid positive participants is 5.7± 2.3 CL/year, consistent with published amyloid accumulation rate of 5.2 ± 1.8 CL/year (Zammit et al, 2024). In the amyloid negative subset, a Wilcoxon signed-rank test revealed no significant differences between PiB-PiB and PiB-NAV in terms of CL difference and rate.
Conclusion: [18F]NAV4694 demonstrated both consistency in trending amyloid accumulation and constancy in sustained amyloid negative participants compared to [11C]PiB. This study highlights the robustness of [18F]NAV4694 CL with a unified processing pipeline and demonstrates how both radiotracers can be integrated within a single analytical framework.