Kinetic modeling and non-invasive approach for translocator protein quantification with 11C-DPA-713

Fumihiko Yasuno; Yasuyuki Kimura; Aya Ogata; Hiroshi Ikenuma; Junichiro Abe; Hiroyuki Minami; Takashi Nihashi; Kastunori Yokoi; Saori Hattori; Nobuyoshi Shimoda; Masanori Ichise; Takashi Sakurai; Kengo Ito; Takashi Kato

doi:10.1016/j.nucmedbio.2022.02.005

Kinetic modeling and non-invasive approach for translocator protein quantification with ¹¹C-DPA-713

Nucl Med Biol. 2022 May-Jun:108-109:76-84. doi: 10.1016/j.nucmedbio.2022.02.005. Epub 2022 Mar 12.

Authors

Affiliations

¹ National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Japan; Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan. Electronic address: yasunof@ncgg.go.jp.
² National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Japan; Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan.
³ Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan; Department of Pharmaceutical, Faculty of Pharmacy, Gifu University of Medical Science, Kani, Japan.
⁴ Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan.
⁵ National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Japan.
⁶ Molecular Analysis Division, Core Facilities, National Center for Geriatrics and Gerontology, Obu, Japan.

PMID: 35349913
DOI: 10.1016/j.nucmedbio.2022.02.005

Abstract

Introduction: ¹¹C-DPA-713 is a positron emission tomography (PET) radiotracer developed for imaging the expression of the translocator protein (TSPO) in glial cells, which is considered to be a marker of the neuroinflammatory burden. This study investigated the pharmacokinetic profile of ¹¹C-DPA-713 and evaluated kinetic modeling and non-invasive TSPO quantification using dynamic PET imaging data in the Alzheimer's disease (AD) and cognitive normal (CN) participants.

Methods: Eleven patients with AD and 6 CN participants were examined using dynamic ¹¹C-DPA-713 PET imaging for 60 min with arterial blood sampling. Time-activity curves were calculated from the cerebellum and three composite regions of interest (ROIs), according to the anatomical definitions of Braak's stages 1 to 3, stage 4, stage 5, and stage 6 that correspond to the pathological stages of tangle deposition. The total distribution volume (V_T) was evaluated using compartmental modeling and graphical analysis. Reference region-based methods were implemented using an optimal area that was assumed to be void of the radiotracer target as reference tissue.

Results: The concentration of radioactivity in plasma demonstrated rapid clearance. ¹¹C-DPA-713 peaked rapidly in the gray matter. Compartmental modeling resulted in a good fit, and the one-tissue model with estimated blood volume correction (1Tv) showed the best performance. The estimated V_T obtained from the graphical plasma methods was highly correlated with that obtained from 1Tv. Reference region-based analysis was conducted using the Braak 6 area as the reference region, and the estimated non-displaceable binding potential was highly correlated with that obtained from 1Tv.

Conclusion: ¹¹C-DPA-713 possesses properties suitable for TSPO quantification with PET imaging. The Braak 6 area was shown to be a useful reference region in the patients with AD and the CN participants, and non-invasive reference tissue models using the Braak 6 area as a reference region can be employed for TSPO quantification with ¹¹C-DPA-713-PET imaging as an alternative to the invasive compartmental model.

Keywords: (11)C-DPA-713; Kinetic modeling; Neuroinflammation; PET; Translocator protein (TSPO).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetamides / metabolism
Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / metabolism
Brain / metabolism
Carrier Proteins / metabolism
Humans
Positron-Emission Tomography / methods
Pyrazoles* / chemistry
Pyrimidines / chemistry
Receptors, GABA / metabolism

Substances

Acetamides
Carrier Proteins
N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide
Pyrazoles
Pyrimidines
Receptors, GABA
TSPO protein, human