Kinetics and 28-day test-retest repeatability and reproducibility of [11C]UCB-J PET brain imaging

Hayel Tuncel; Ronald Boellaard; Emma M Coomans; Erik Fj de Vries; Andor Wjm Glaudemans; Paula Kopschina Feltes; David V García; Sander Cj Verfaillie; Emma E Wolters; Steven P Sweeney; J Michael Ryan; Magnus Ivarsson; Berkley A Lynch; Patrick Schober; Philip Scheltens; Robert C Schuit; Albert D Windhorst; Peter P De Deyn; Bart Nm van Berckel; Sandeep Sv Golla

doi:10.1177/0271678X20964248

Kinetics and 28-day test-retest repeatability and reproducibility of [11C]UCB-J PET brain imaging

Hayel Tuncel, Ronald Boellaard, Emma M Coomans, Erik Fj de Vries, Andor Wjm Glaudemans, Paula Kopschina Feltes, David V García, Sander Cj Verfaillie, Emma E Wolters, Steven P Sweeney, J Michael Ryan, Magnus Ivarsson, Berkley A Lynch, Patrick Schober, Philip Scheltens, Robert C Schuit, Albert D Windhorst, Peter P De Deyn, Bart Nm van Berckel, Sandeep Sv Golla

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

[11C]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test-retest repeatability (TRT) of quantitative [11C]UCB-J brain positron emission tomography (PET) imaging in Alzheimer's disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [11C]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K1) and volume of distribution (VT) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_VB and 2T4k_VB described the [11C]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for VT, DVR and SRTM BPND were -2.2% ± 8.5, 0.4% ± 12.0 and -8.0% ± 10.2, averaged over all subjects. [11C]UCB-J kinetics can be well described by a 1T2k_VB model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for VT, DVR and BPND was <15% (1SD) averaged over all subjects and indicates adequate quantitative repeatability of [11C]UCB-J PET.

Original language	English
Pages (from-to)	1338-1350
Number of pages	13
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	41
Issue number	6
Early online date	2020
DOIs	https://doi.org/10.1177/0271678X20964248 https://doi.org/10.1177/0271678X20964248
Publication status	Published - Jun 2021

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Tuncel, H., Boellaard, R., Coomans, E. M., de Vries, E. F., Glaudemans, A. W., Feltes, P. K., García, D. V., Verfaillie, S. C., Wolters, E. E., Sweeney, S. P., Ryan, J. M., Ivarsson, M., Lynch, B. A., Schober, P., Scheltens, P., Schuit, R. C., Windhorst, A. D., De Deyn, P. P., van Berckel, B. N., & Golla, S. S. (2021). Kinetics and 28-day test-retest repeatability and reproducibility of [11C]UCB-J PET brain imaging. Journal of Cerebral Blood Flow and Metabolism, 41(6), 1338-1350. https://doi.org/10.1177/0271678X20964248, https://doi.org/10.1177/0271678X20964248

Tuncel, Hayel ; Boellaard, Ronald ; Coomans, Emma M ; de Vries, Erik Fj ; Glaudemans, Andor Wjm ; Feltes, Paula Kopschina ; García, David V ; Verfaillie, Sander Cj ; Wolters, Emma E ; Sweeney, Steven P ; Ryan, J Michael ; Ivarsson, Magnus ; Lynch, Berkley A ; Schober, Patrick ; Scheltens, Philip ; Schuit, Robert C ; Windhorst, Albert D ; De Deyn, Peter P ; van Berckel, Bart Nm ; Golla, Sandeep Sv. / Kinetics and 28-day test-retest repeatability and reproducibility of [11C]UCB-J PET brain imaging. In: Journal of Cerebral Blood Flow and Metabolism. 2021 ; Vol. 41, No. 6. pp. 1338-1350.

@article{ad95a11e735944fab98b27da2751a881,

title = "Kinetics and 28-day test-retest repeatability and reproducibility of [11C]UCB-J PET brain imaging",

abstract = "[11C]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test-retest repeatability (TRT) of quantitative [11C]UCB-J brain positron emission tomography (PET) imaging in Alzheimer's disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [11C]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K1) and volume of distribution (VT) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_VB and 2T4k_VB described the [11C]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for VT, DVR and SRTM BPND were -2.2% ± 8.5, 0.4% ± 12.0 and -8.0% ± 10.2, averaged over all subjects. [11C]UCB-J kinetics can be well described by a 1T2k_VB model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for VT, DVR and BPND was <15% (1SD) averaged over all subjects and indicates adequate quantitative repeatability of [11C]UCB-J PET.",

keywords = "Aged, Aged, 80 and over, Alzheimer Disease/diagnostic imaging, Female, Humans, Image Interpretation, Computer-Assisted, Kinetics, Male, Membrane Glycoproteins/metabolism, Middle Aged, Nerve Tissue Proteins/metabolism, Neuroimaging/methods, Positron-Emission Tomography/methods, Pyridines/pharmacokinetics, Pyrrolidinones/pharmacokinetics, Radiopharmaceuticals/pharmacokinetics, Reproducibility of Results",

author = "Hayel Tuncel and Ronald Boellaard and Coomans, {Emma M} and {de Vries}, {Erik Fj} and Glaudemans, {Andor Wjm} and Feltes, {Paula Kopschina} and Garc{\'i}a, {David V} and Verfaillie, {Sander Cj} and Wolters, {Emma E} and Sweeney, {Steven P} and Ryan, {J Michael} and Magnus Ivarsson and Lynch, {Berkley A} and Patrick Schober and Philip Scheltens and Schuit, {Robert C} and Windhorst, {Albert D} and {De Deyn}, {Peter P} and {van Berckel}, {Bart Nm} and Golla, {Sandeep Sv}",

note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was made possible by Rodin Therapeutics Inc. by providing funding for the study. Publisher Copyright: {\textcopyright} The Author(s) 2020.",

year = "2021",

month = jun,

doi = "10.1177/0271678X20964248",

language = "English",

volume = "41",

pages = "1338--1350",

journal = "Journal of Cerebral Blood Flow and Metabolism",

issn = "0271-678X",

publisher = "Nature Publishing Group",

number = "6",

}

Tuncel, H , Boellaard, R , Coomans, EM, de Vries, EF, Glaudemans, AW, Feltes, PK, García, DV, Verfaillie, SC, Wolters, EE, Sweeney, SP, Ryan, JM, Ivarsson, M, Lynch, BA, Schober, P , Scheltens, P , Schuit, RC , Windhorst, AD, De Deyn, PP, van Berckel, BN & Golla, SS 2021, 'Kinetics and 28-day test-retest repeatability and reproducibility of [11C]UCB-J PET brain imaging', Journal of Cerebral Blood Flow and Metabolism, vol. 41, no. 6, pp. 1338-1350. https://doi.org/10.1177/0271678X20964248, https://doi.org/10.1177/0271678X20964248

Kinetics and 28-day test-retest repeatability and reproducibility of [11C]UCB-J PET brain imaging. / Tuncel, Hayel ; Boellaard, Ronald ; Coomans, Emma M; de Vries, Erik Fj; Glaudemans, Andor Wjm; Feltes, Paula Kopschina; García, David V; Verfaillie, Sander Cj; Wolters, Emma E; Sweeney, Steven P; Ryan, J Michael; Ivarsson, Magnus; Lynch, Berkley A; Schober, Patrick ; Scheltens, Philip ; Schuit, Robert C ; Windhorst, Albert D; De Deyn, Peter P; van Berckel, Bart Nm ; Golla, Sandeep Sv.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 41, No. 6, 06.2021, p. 1338-1350.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Kinetics and 28-day test-retest repeatability and reproducibility of [11C]UCB-J PET brain imaging

AU - Tuncel, Hayel

AU - Boellaard, Ronald

AU - Coomans, Emma M

AU - de Vries, Erik Fj

AU - Glaudemans, Andor Wjm

AU - Feltes, Paula Kopschina

AU - García, David V

AU - Verfaillie, Sander Cj

AU - Wolters, Emma E

AU - Sweeney, Steven P

AU - Ryan, J Michael

AU - Ivarsson, Magnus

AU - Lynch, Berkley A

AU - Schober, Patrick

AU - Scheltens, Philip

AU - Schuit, Robert C

AU - Windhorst, Albert D

AU - De Deyn, Peter P

AU - van Berckel, Bart Nm

AU - Golla, Sandeep Sv

N1 - Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was made possible by Rodin Therapeutics Inc. by providing funding for the study. Publisher Copyright: © The Author(s) 2020.

PY - 2021/6

Y1 - 2021/6

N2 - [11C]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test-retest repeatability (TRT) of quantitative [11C]UCB-J brain positron emission tomography (PET) imaging in Alzheimer's disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [11C]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K1) and volume of distribution (VT) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_VB and 2T4k_VB described the [11C]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for VT, DVR and SRTM BPND were -2.2% ± 8.5, 0.4% ± 12.0 and -8.0% ± 10.2, averaged over all subjects. [11C]UCB-J kinetics can be well described by a 1T2k_VB model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for VT, DVR and BPND was <15% (1SD) averaged over all subjects and indicates adequate quantitative repeatability of [11C]UCB-J PET.

AB - [11C]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test-retest repeatability (TRT) of quantitative [11C]UCB-J brain positron emission tomography (PET) imaging in Alzheimer's disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [11C]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K1) and volume of distribution (VT) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_VB and 2T4k_VB described the [11C]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for VT, DVR and SRTM BPND were -2.2% ± 8.5, 0.4% ± 12.0 and -8.0% ± 10.2, averaged over all subjects. [11C]UCB-J kinetics can be well described by a 1T2k_VB model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for VT, DVR and BPND was <15% (1SD) averaged over all subjects and indicates adequate quantitative repeatability of [11C]UCB-J PET.

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease/diagnostic imaging

KW - Female

KW - Humans

KW - Image Interpretation, Computer-Assisted

KW - Kinetics

KW - Male

KW - Membrane Glycoproteins/metabolism

KW - Middle Aged

KW - Nerve Tissue Proteins/metabolism

KW - Neuroimaging/methods

KW - Positron-Emission Tomography/methods

KW - Pyridines/pharmacokinetics

KW - Pyrrolidinones/pharmacokinetics

KW - Radiopharmaceuticals/pharmacokinetics

KW - Reproducibility of Results

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U2 - 10.1177/0271678X20964248

DO - 10.1177/0271678X20964248

M3 - Article

C2 - 34013797

VL - 41

SP - 1338

EP - 1350

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 6

ER -

Kinetics and 28-day test-retest repeatability and reproducibility of [11C]UCB-J PET brain imaging

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