Quantification of TSPO overexpression in a rat model of local neuroinflammation induced by intracerebral injection of LPS by the use of [(18)F]DPA-714 PET.
OBJECTIVE
[(18)F]DPA-714 is a radiotracer with high affinity for TSPO. We have characterized the kinetics of [(18)F]DPA-714 in rat brain and evaluated its ability to quantify TSPO expression with PET using a neuroinflammation model induced by unilateral intracerebral injection of lipopolysaccharide (LPS).


METHODS
Dynamic small-animal PET scans with [(18)F]DPA-714 were performed in Wistar rats on a FOCUS-220 system for up to 3 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Full kinetic modelling of [(18)F]DPA-714 brain uptake was performed using a metabolite-corrected arterial plasma input function. Binding potential (BPND) calculated as the distribution volume ratio minus one (DVR-1) between affected and healthy brain tissue was used as the outcome measure and evaluated against reference tissue models.


RESULTS
The percentage of intact [(18)F]DPA-714 in arterial plasma samples was 92 ± 4 % at 10 min, 75 ± 8 % at 40 min and 52 ± 6 % at 180 min. The radiometabolite fraction in brain was negligible (<3 % at 30 min). Among the models investigated, the reversible two-tissue (2T) compartment model best described [(18)F]DPA-714 brain kinetics. BPND values obtained with a simplified and a multilinear reference tissue model (SRTM, MRTM) using the contralateral striatum as the reference region correlated well (Spearman's r = 0.96, p ≤ 0.003) with 2T BPND values calculated as DVR-1, and showed comparable bias (bias range 17.94 %, 20.32 %). Analysis of stability over time suggested that the acquisition time should be at least 90 min for SRTM and MRTM.


CONCLUSIONS
Quantification of [(18)F]DPA-714 binding to TSPO with full kinetic modelling is feasible using a 2T model. SRTM and MRTM can be suggested as reasonable substitutes with the contralateral striatum as the reference region and a scan duration of at least 90 min. However, selection of the reference region depends on the disease model used.
Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Campus Gasthuisberg O&N2, Herestraat 49 Box 821, BE-3000, Leuven, Belgium.
Dieter
D
Ory
Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital and KU Leuven, Leuven, Belgium.
Andrey
A
Postnov
Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital and KU Leuven, Leuven, Belgium.
Michel
M
Koole
Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Campus Gasthuisberg O&N2, Herestraat 49 Box 821, BE-3000, Leuven, Belgium.
Sofie
S
Celen
Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital and KU Leuven, Leuven, Belgium.
Bart
B
de Laat
Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Campus Gasthuisberg O&N2, Herestraat 49 Box 821, BE-3000, Leuven, Belgium.
Alfons
A
Verbruggen
Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital and KU Leuven, Leuven, Belgium.
Koen
K
Van Laere
Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Campus Gasthuisberg O&N2, Herestraat 49 Box 821, BE-3000, Leuven, Belgium. Guy.Bormans@pharm.kuleuven.be.
Guy
G
Bormans
Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital and KU Leuven, Leuven, Belgium.
Cindy
C
Casteels
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005462:Fluorine Radioisotopes; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism; D007267:Injections; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D011720:Pyrazoles; D011743:Pyrimidines; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*
D002352:Carrier Proteins; D005462:Fluorine Radioisotopes; D008070:Lipopolysaccharides; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D011963:Receptors, GABA-A; C069997:Tspo protein, rat
Kinetic analysis; Rat; Small-animal PET; TSPO; [18F]DPA-714