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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-09-2020 | Alzheimer's Disease | Original Article

PET imaging of beta-secretase 1 in the human brain: radiation dosimetry, quantification, and test-retest examination of [¹⁸F]PF-06684511

Authors: Ryosuke Arakawa, Akihiro Takano, Per Stenkrona, Vladimir Stepanov, Sangram Nag, Mahabuba Jahan, Per Grybäck, Martin Bolin, Laigao Chen, Lei Zhang, Ping He, Anabella Villalobos, Timothy J. McCarthy, Christer Halldin, Andrea Varrone

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 10/2020

Abstract

Purpose

Beta-secretase 1 (BACE1) enzyme is implicated in the pathophysiology of Alzheimer’s disease. [¹⁸F]PF-06684511 is a positron emission tomography (PET) radioligand for imaging BACE1. Despite favorable brain kinetic properties, the effective dose (ED) of [¹⁸F]PF-06684511 estimated in non-human primates was relatively high. This study was therefore designed to evaluate the whole-body distribution, dosimetry, quantification, and test-retest reliability of imaging brain BACE1 with [¹⁸F]PF-06684511 in healthy volunteers.

Methods

Five subjects were studied for the dosimetry study. Whole-body PET was performed for 366 min with 4 PET-CT sessions. Estimates of the absorbed radiation dose were calculated using the male adult model. Eight subjects participated in the test-retest study. Brain PET measurements were conducted for 123 min with an interval of 5 to 19 days between test and retest conditions. The total distribution volume (V_T) was estimated with one-tissue (1T), two-tissue (2T), compartment model (CM), and graphical analysis. Test-retest variability (TRV) and intraclass correlation coefficient (ICC) of V_T were calculated as reliability measures.

Results

In the dosimetry study, the highest uptake was found in the liver (25.2 ± 2.3 %ID at 0.5 h) and the largest dose was observed in the pancreas (92.9 ± 52.2 μSv/MBq). The calculated ED was 24.7 ± 0.8 μSv/MBq. In the test-retest study, 2TCM described the time-activity curves well. V_T (2TCM) was the highest in the anterior cingulate cortex (6.28 ± 1.09 and 6.85 ± 0.81) and the lowest in the cerebellum (4.23 ± 0.88 and 4.20 ± 0.75). Mean TRV and ICC of V_T (2TCM) were 16.5% (12.4–20.5%) and 0.496 (0.291–0.644).

Conclusion

The ED of [¹⁸F]PF-06684511 was similar to other ¹⁸F radioligands, allowing repeated PET measurements. 2TCM was the most appropriate quantification method. TRV of V_T was similar to other radioligands without a reference region, albeit with lower ICC. These data indicated that [¹⁸F]PF-06684511 is a suitable radioligand to measure BACE1 level in the human brain.

Trial registration

EudraCT 2016-001110-19 (registered 2016-08-08)

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Title: PET imaging of beta-secretase 1 in the human brain: radiation dosimetry, quantification, and test-retest examination of [18F]PF-06684511
Authors: Ryosuke Arakawa
Akihiro Takano
Per Stenkrona
Vladimir Stepanov
Sangram Nag
Mahabuba Jahan
Per Grybäck
Martin Bolin
Laigao Chen
Lei Zhang
Ping He
Anabella Villalobos
Timothy J. McCarthy
Christer Halldin
Andrea Varrone
Publication date: 01-09-2020
Publisher: Springer Berlin Heidelberg
Keywords: Alzheimer's Disease
Positron Emission Tomography
Alzheimer's Disease
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 10/2020
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-020-04739-5

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PET imaging of beta-secretase 1 in the human brain: radiation dosimetry, quantification, and test-retest examination of [¹⁸F]PF-06684511

Abstract

Purpose

Methods

Results

Conclusion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Trial registration

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