Evaluation of [18F]-JNJ-64326067-AAA tau PET tracer in humans

Abstract

The [¹⁸F]-JNJ-64326067-AAA ([¹⁸F]-JNJ-067) tau tracer was evaluated in healthy older controls (HCs), mild cognitive impairment (MCI), Alzheimer's disease (AD), and progressive supranuclear palsy (PSP) participants. Seventeen subjects (4 HCs, 5 MCIs, 5 ADs, and 3 PSPs) received a [¹¹C]-PIB amyloid PET scan, and a tau [¹⁸F]-JNJ-067 PET scan 0-90 minutes post-injection. Only MCIs and ADs were amyloid positive. The simplified reference tissue model, Logan graphical analysis distribution volume ratio, and SUVR were evaluated for quantification. The [¹⁸F]-JNJ-067 tau signal relative to the reference region continued to increase to 90 min, indicating the tracer had not reached steady state. There was no significant difference in any bilateral ROIs for MCIs or PSPs relative to HCs; AD participants showed elevated tracer relative to controls in most cortical ROIs (P < 0.05). Only AD participants showed elevated retention in the entorhinal cortex. There was off-target signal in the putamen, pallidum, thalamus, midbrain, superior cerebellar gray, and white matter. [¹⁸F]-JNJ-067 significantly correlated (p < 0.05) with Mini-Mental State Exam in entorhinal cortex and temporal meta regions. There is clear binding of [¹⁸F]-JNJ-067 in AD participants. Lack of binding in HCs, MCIs and PSPs suggests [¹⁸F]-JNJ-067 may not bind to low levels of AD-related tau or 4 R tau.

Keywords: Aging; Alzheimer’s disease; PET; [18F]-JNJ-067; tau.

Figure 1.

Plots are time activity curves (TACs; a, c, e, g) and standardized uptake value ratios (SUVRs; b, d, f, h) for [¹⁸F]-JNJ-067. The data shown are from HC1 (a-b), MCI1 (c-d), AD1 (e-f), and PSP3 (g-h) (Table 1); all TACs and SUVRs are representative of their diagnostic groups except for MCI1 who had the greatest average mean cortical [¹⁸F]-JNJ-067 binding of all MCIs. The points represent mean PET values. The colored lines in a, c, e, and g are SRTM fits to the data. The lines in b, d, f and h just connect the individual points.

Figure 2.

Correlation between DVR and SRTM BP_ND+1 (a) and DVR and SUVR_70-90 (b) in 36 bilateral cortical ROIs across 17 subjects. Both correlations are significant (p<0.001) after Bonferroni correction.

Figure 3.

[¹⁸F]-JNJ-067 DVR images (k_2ref = 0.025 min⁻¹; 35–90 min) warped to template space. Each column is a different subject following the order from Table 1, rows go through axial slices equally spaced for each subject ending with coronal showing entorhinal cortex.

Figure 4.

Mean [¹⁸F]-JNJ-067 DVR values. Bars are ordered by HC (orange), MCI (purple), AD (green), and PSP (blue) subjects, and ordered within diagnosis group by increasing PIB SUVR index (as in Table 1).

Figure 5.

(a) [¹⁸F]-JNJ-067 DVRs in regions that show off-target signal in other tau tracers. Bars are ordered by HC (orange), MCI (purple), AD (green), and PSP (blue) subjects, and ordered within diagnosis group by increasing PIB SUVR index (as in Table 1). (b) Mean of 4 HC subjects in template space showing regions of potential off-target signal.

Figure 6.

[¹⁸F]-JNJ-067 entorhinal cortex DVR vs MMSE (circles; r = −0.52; p < 0.05) and temporal meta ROI vs MMSE (squares, r= −0.56; p < 0.05).