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Comparative Study
. 2017 Jun;58(6):996-1002.
doi: 10.2967/jnumed.116.182980. Epub 2016 Nov 10.

In Vivo Comparison of Tau Radioligands 18F-THK-5351 and 18F-THK-5317

Tobey J Betthauser  1   2 , Patrick J Lao  3   2 , Dhanabalan Murali  3 , Todd E Barnhart  3 , Shozo Furumoto  4 , Nobuyuki Okamura  5 , Charles K Stone  6 , Sterling C Johnson  7   8 , Bradley T Christian  3   2
Affiliations
Comparative Study

In Vivo Comparison of Tau Radioligands 18F-THK-5351 and 18F-THK-5317

Tobey J Betthauser et al. J Nucl Med. 2017 Jun.

Abstract

This study compared the in vivo imaging characteristics of tau PET ligands 18F-THK-5351 and 18F-THK-5317 in the context of Alzheimer disease (AD). Additionally, reference tissue distribution volume ratio (DVR) estimation methods and SUV ratio (SUVR) timing windows were evaluated to determine the optimal strategy for specific binding quantification. Methods: Twenty-eight subjects (mean age ± SD, 71 ± 7 y) underwent either dynamic 90-min 18F-THK-5317 or 18F-THK-5351 PET scans. Bland-Altman plots were used to compare the simplified reference tissue method, multilinear reference tissue method (MRTM2), and Logan reference tissue DVR estimates and to assess temporal stability of SUVR windows using cerebellar gray matter as a reference region. In vivo kinetics and DVR estimates were directly compared for 10 subjects who underwent both 18F-THK-5317 and 18F-THK-5351 PET scans. Results: THK-5351 exhibited faster cerebellar gray matter clearance, faster cortical white matter clearance, and higher DVR estimates in AD tau-associated regions of interest than THK-5317. The MRTM2 method produced the most reliable DVR estimates for both tracers, particularly when scan duration was shortened to 60 min. SUVR stability was observed 50-70 min after injection for both tracers. Parametric images revealed differences between MRTM2, Logan, and SUVR binding in white matter regions for THK-5317. Conclusion: THK-5317 and THK-5351 show promise for in vivo detection of AD tau. THK-5351 has more favorable pharmacokinetics and imaging characteristics than THK-5317.

Keywords: Alzheimer’s disease; THK; positron emission tomography; quantitation; tau.

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Figures

FIGURE 1.
FIGURE 1.
Mean SUVs and target–to–cerebellar GM plots comparing THK-5317 and THK-5351. Error bars represent 95% confidence interval across 10 subjects scanned with both tracers. %ID = percentage injected dose; Cbm = cerebellum; Hipp = hippocampus; ITG = inferior temporal gyrus; wt = weight.
FIGURE 2.
FIGURE 2.
Comparison of DVR estimates for SRTM, MRTM2, and Logan with the mean (μ) and SD (σ) of difference between methods.
FIGURE 3.
FIGURE 3.
Comparison of MRTM2 (top) and Logan (bottom) DVR estimates determined with truncated scanning durations compared with full 90-min dataset with t* = 30 min for THK-5351.
FIGURE 4.
FIGURE 4.
Regression of THK-5351 SUVR on 90-min MRTM2 (t* = 30 min) DVR estimates. DVR SUVR regressions and SUVR stability for other SUVR windows and for THK-5317 are located in Supplemental Figures 6 and 7.
FIGURE 5.
FIGURE 5.
Comparison of MRTM2 and Logan DVR and SUVR (50–70 min) parametric images for THK-5351 (top) and THK-5317 (bottom) in 81-y-old man with MCI (Mini–Mental State Examination = 28). THK-5351 (392 MBq) scan was 342 d after THK-5317 (200 MBq).
FIGURE 6.
FIGURE 6.
Comparison of THK-5317 and THK-5351 DVR estimates using MRTM2 (truncated 60-min data and t* = 30 min).
See this image and copyright information in PMC

References

    1. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol (Berl). 1991;82:239–259. - PubMed
    1. Thal DR, Rüb U, Orantes M, Braak H. Phases of Aβ-deposition in the human brain and its relevance for the development of AD. Neurology. 2002;58:1791–1800. - PubMed
    1. Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011;70:960–969. - PubMed
    1. Gómez-Isla T, Price JL, McKeel DW, Jr, Morris JC, Growdon JH, Hyman BT. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer’s disease. J Neurosci. 1996;16:4491–4500. - PMC - PubMed
    1. Guillozet AL, Weintraub S, Mash DC, Mesulam MM. Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. Arch Neurol. 2003;60:729–736. - PubMed

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