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Clinical and Translational Imaging

, Volume 3, Issue 6, pp 403–416 | Cite as

Challenges of quantification of TSPO in the human brain

  • Rainer Hinz
  • Ronald Boellaard
Review Article

Abstract

The first positron emission tomography (PET) imaging studies in humans of the translocator protein 18 kDa (TSPO) were conducted in the 1980s with a primary interest in quantifying the binding in peripheral organs such as the heart, spleen and kidneys to what was then known as the peripheral benzodiazepine receptor. However, the number of studies rapidly increased when the focus of the research shifted to the brain, and [11C](R)-PK11195 became de facto the reference radiotracer for all in vivo TSPO binding assays. For the quantitative analysis of the data which initially was performed with compartmental models and plasma input functions, this led to the adoption of the reference tissue kinetic models which were developed at the same time in the mid 1990s. In contrast to many neuro-receptor studies of the dopaminergic or serotonergic system, it was not possible to anatomically define a brain region devoid of TSPO that could serve as a reference region. Instead, data-driven techniques were adopted that extracted at the voxel level reference tissue kinetics without incorporating anatomical information. In this review, an overview of the development, use and challenges of the various quantitative analysis methods for TSPO brain PET data is given. The different approaches to (automatically) extract reference tissue input curves from the dynamic images are discussed. Descriptions of key PET imaging studies exploring TSPO binding quantitatively in disease populations are included.

Keywords

Positron emission tomography (PET) Quantification [11C]PK11195 Translocator protein 18 kDa (TSPO) 

Abbreviations

AD

Alzheimer’s disease

Bavail

Density of sites available to bind radioligand in vivo

BBB

Blood–brain barrier

BF

Blood flow

BP

Binding potential

BPF

Binding potential relative to the free ligand concentration in plasma

BPND

Binding potential relative to the non-displaceable binding in tissue

CBF

Cerebral blood flow

CNS

Central nervous system

CT

Computed tomography

HAB

High-affinity binder

HD

Huntington’s disease

HPLC

High-performance liquid chromatography

HHRT

High Resolution Research Tomograph

INMiND

Imaging of neuroinflammation in neurodegenerative diseases

KD

Dissociation constant

LAB

Low-affinity binder

MAB

Mixed affinity binder

MCI

Mild cognitive impairment

MRI

Magnetic resonance imaging

PET

Positron emission tomography

PK11195

1-(2-Chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide

PVE

Partial volume effect

ROI

Region of interest

SD

Standard deviation

SPE

Solid-phase extraction

SRTM

Simplified reference tissue model

SRTMV

Simplified reference tissue model with vascular component

SUV

Standard uptake value

SVCA4

Supervised cluster analysis with four kinetic classes

SVCA6

Supervised cluster analysis with six kinetic classes

TAC

Time–activity curve

TLC

Thin-layer chromatography

TSPO

Translocator protein 18 kDa

VND

Non-displaceable volume of distribution

VT

Total volume of distribution

Notes

Acknowledgments

We gratefully acknowledge Christian Prenant and Gavin D. Brown for their explanations provided on the radiochemistry, David J. Brooks for the invitation to Århus and the stimulating discussions on [11C](R)-PK11195 data analysis there, Federico Roncaroli for his advice on neuropathological data and the European Union’s Seventh Framework Programme (FP7/2007-2013) for financial support under the Grant agreement HEALTH-F2-2011-278850 (Imaging of Neuroinflammation in Neurodegenerative Diseases) bringing the INMiND consortium together.

Authors’ contributions

R Hinz: Design and content planning of the article; literature search and review; manuscript writing, formatting and editing; correspondence with the editorial office. R Boellaard: Design and content planning of the article; literature search and review; manuscript writing and editing; data processing for the preparation of the figures.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval and informed consent

All procedures performed in studies, with human participants, in which the authors were involved, were conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in those studies.

Human rights and animal standards

This review article does not contain studies with animals performed by any of the authors.

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Copyright information

© Italian Association of Nuclear Medicine and Molecular Imaging 2015

Authors and Affiliations

  1. 1.Wolfson Molecular Imaging CentreUniversity of ManchesterManchesterUK
  2. 2.Department of Radiology and Nuclear MedicineVU University Medical CenterAmsterdamThe Netherlands

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