title: Quantification of [18F]DPA-714 binding in the human brain: initial studies in healthy controls and Alzheimer's disease patients.
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.
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Sandeep S V
authors: SS
authors: Golla
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Ronald
authors: R
authors: Boellaard
authors: Division of Clinical Neurosciences, Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
authors: Vesa
authors: V
authors: Oikonen
authors: Bayer HealthCare AG, Berlin, Germany.
authors: Anja
authors: A
authors: Hoffmann
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Bart N M
authors: BN
authors: van Berckel
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Albert D
authors: AD
authors: Windhorst
authors: Division of Clinical Neurosciences, Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
authors: Jere
authors: J
authors: Virta
authors: Division of Clinical Neurosciences, Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
authors: Merja
authors: M
authors: Haaparanta-Solin
authors: Division of Clinical Neurosciences, Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
authors: Pauliina
authors: P
authors: Luoto
authors: Division of Clinical Neurosciences, Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
authors: Nina
authors: N
authors: Savisto
authors: Division of Clinical Neurosciences, Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
authors: Olof
authors: O
authors: Solin
authors: Bayer HealthCare AG, Berlin, Germany.
authors: Ray
authors: R
authors: Valencia
authors: Bayer HealthCare AG, Berlin, Germany.
authors: Andrea
authors: A
authors: Thiele
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Jonas
authors: J
authors: Eriksson
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Robert C
authors: RC
authors: Schuit
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Adriaan A
authors: AA
authors: Lammertsma
authors: Division of Clinical Neurosciences, Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
authors: Juha O
authors: JO
authors: Rinne
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D011859:Radiography; D018079:Receptors, GABA / Q000378:metabolism*; D013997:Time Factors
chemical_list: D005462:Fluorine Radioisotopes; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D018079:Receptors, GABA; C499229:TSPO protein, human
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