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

Journal: Nuclear medicine and biology 2022;108-109():76-84

PMID: 35349913

Full Text on Elsevier Science View on PubMed

Abstract

INTRODUCTION

C-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 C-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 C-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) 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. C-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 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

C-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 C-DPA-713-PET imaging as an alternative to the invasive compartmental model.

Address: 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: [email protected].; 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.; 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.; Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan.; National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Japan.; Molecular Analysis Division, Core Facilities, National Center for Geriatrics and Gerontology, Obu, Japan.

DOI: 10.1016/j.nucmedbio.2022.02.005

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MeSH Terms: Acetamides, Alzheimer Disease, Brain, Carrier Proteins, Humans, Positron-Emission Tomography, Pyrazoles, Pyrimidines, Receptors, GABA