Quantification of [18F]DPA-714 Binding in the Human Brain: Initial Studies in Healthy Controls and Alzheimer'S Disease Patients

• Published in: Journal of cerebral blood flow and metabolism Vol. 35; no. 5; pp. 766 - 772
• Main Authors: Golla, Sandeep SV, Boellaard, Ronald, Oikonen, Vesa, Hoffmann, Anja, van Berckel, Bart NM, Windhorst, Albert D, Virta, Jere, Haaparanta-Solin, Merja, Luoto, Pauliina, Savisto, Nina, Solin, Olof, Valencia, Ray, Thiele, Andrea, Eriksson, Jonas, Schuit, Robert C, Lammertsma, Adriaan A, Rinne, Juha O
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.05.2015; Sage Publications Ltd; Nature Publishing Group
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Female; Fluorine Radioisotopes - administration & dosage; Fluorine Radioisotopes - pharmacokinetics; Humans; Kinetics; Male; Middle Aged; Models, Biological; Original; Positron-Emission Tomography; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Radiography; Receptors, GABA - metabolism; Time Factors; TSPO; [18F]DPA-714; neuroinflammation; Alzheimer's disease; PET quantification
• ISSN: 0271-678X; 1559-7016; 1559-7016
• DOI: 10.1038/jcbfm.2014.261

Fluorine-18 labelled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide ([18F] 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 [18F]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 [18F]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 [18F]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 [18F]DPA-714 cannot be used for separating individual AD patients from heathy subjects, but further studies including TSPO binding status are needed to substantiate these findings.