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Randomized Controlled Trial
. 2015 May;35(5):766-72.
doi: 10.1038/jcbfm.2014.261. Epub 2015 Feb 4.

Quantification of [18F]DPA-714 binding in the human brain: initial studies in healthy controls and Alzheimer's disease patients

Sandeep S V Golla  1 , Ronald Boellaard  1 , Vesa Oikonen  2 , Anja Hoffmann  3 , Bart N M van Berckel  1 , Albert D Windhorst  1 , Jere Virta  2 , Merja Haaparanta-Solin  2 , Pauliina Luoto  2 , Nina Savisto  2 , Olof Solin  2 , Ray Valencia  3 , Andrea Thiele  3 , Jonas Eriksson  1 , Robert C Schuit  1 , Adriaan A Lammertsma  1 , Juha O Rinne  2
Affiliations
Randomized Controlled Trial

Quantification of [18F]DPA-714 binding in the human brain: initial studies in healthy controls and Alzheimer's disease patients

Sandeep S V Golla et al. J Cereb Blood Flow Metab. 2015 May.

Abstract

Fluorine-18 labelled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide ([(18)F]DPA-714) binds to the 18-kDa translocator protein (TSPO) with high affinity. The aim of this initial methodological study was to develop a plasma input tracer kinetic model for quantification of [(18)F]DPA-714 binding in healthy subjects and Alzheimer's disease (AD) patients, and to provide a preliminary assessment whether there is a disease-related signal. Ten AD patients and six healthy subjects underwent a dynamic positron emission tomography (PET) study along with arterial sampling and a scan protocol of 150 minutes after administration of 250 ± 10 MBq [(18)F]DPA-714. The model that provided the best fits to tissue time activity curves (TACs) was selected based on Akaike Information Criterion and F-test. The reversible two tissue compartment plasma input model with blood volume parameter was the preferred model for quantification of [(18)F]DPA-714 kinetics, irrespective of scan duration, volume of interest, and underlying volume of distribution (VT). Simplified reference tissue model (SRTM)-derived binding potential (BPND) using cerebellar gray matter as reference tissue correlated well with plasma input-based distribution volume ratio (DVR). These data suggest that [(18)F]DPA-714 cannot be used for separating individual AD patients from healthy subjects, but further studies including TSPO binding status are needed to substantiate these findings.

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Figures

Figure 1
Figure 1
Histograms indicating number of selections (y axis) per model (x axis) according to the Akaike criterion for (A) subjects, (B) regions, (C) regions according to size and (D) varying volumes of distribution (VT).
Figure 2
Figure 2
Kinetic parameter values (VT, K1, plasma input-derived nondisplaceable binding potential (BPND) and simplified reference tissue model (SRTM)-derived BPND) for different scan durations plotted against those obtained for 90 minutes of positron emission tomography (PET) data.
Figure 3
Figure 3
Validation of simplified reference tissue model (SRTM) using cerebellum as a reference region: comparison of plasma input modelling-based distribution volume ratio (DVR)-1 with SRTM-based nondisplaceable binding potential (BPND) for (a) the total gray matter volume of interest (VOI) and (b) all gray-matter VOIs. LOI is the line of identity.
Figure 4
Figure 4
Total gray matter VT, nondisplaceable binding potential (BPND) and K1 for both healthy subjects and Alzheimer's disease (AD) patients.
See this image and copyright information in PMC

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