PURPOSE: We aimed to characterize pharmacologically the TSPO- radioligand [(18)F]DPA-714 in the brain of healthy cynomolgus monkeys and evaluate the cellular origin of its binding in a model of neurodegeneration induced by intrastriatal injection of quinolinic acid (QA). METHODS: [(18)F]DPA-714 PET images were acquired before and at 2, 7, 14, 21, 49, 70, 91 days after putaminal lesioning. Blocking and displacement studies were carried out (PK11195). Different modelling approaches estimated rate constants and V T (total distribution volume) which was used to measure longitudinal changes in the lesioned putamen. Sections for immunohistochemical labelling were prepared at the same time-points to evaluate correlations between in vivo [(18)F]DPA-714 binding and microglial/astrocytic activation. RESULTS: [(18)F]DPA-714 showed a widespread distribution with a higher signal in the thalamus and occipital cortex and lower binding in the cerebellum. TSPO was expressed throughout the whole brain and about 73 % of [(18)F]DPA-714 binding was specific for TSPO in vivo. The one-tissue compartment model (1-TCM) provided good and reproducible estimates of V T and rate constants, and V T values from the 1-TCM and the Logan approach were highly correlated (r (2) = 0.85). QA lesioning induced an increase in V T, which was +17 %, +54 %, +157 % and +39 % higher than baseline on days 7, 14, 21 and 91 after QA injection, respectively. Immunohistochemistry revealed an early microglial and a delayed astrocytic activation after QA injection. [(18)F]DPA-714 binding matched TSPO immunopositive areas and showed a stronger colocalization with CD68 microglia than with GFAP-activated astrocytes. CONCLUSION: [(18)F]DPA-714 binds to TSPO with high specificity in the primate brain under normal conditions and in the QA model. This tracer provides a sensitive tool for assessing neuroinflammation in the human brain.
PURPOSE: We aimed to characterize pharmacologically the TSPO- radioligand [(18)F]DPA-714 in the brain of healthy cynomolgus monkeys and evaluate the cellular origin of its binding in a model of neurodegeneration induced by intrastriatal injection of quinolinic acid (QA). METHODS: [(18)F]DPA-714 PET images were acquired before and at 2, 7, 14, 21, 49, 70, 91 days after putaminal lesioning. Blocking and displacement studies were carried out (PK11195). Different modelling approaches estimated rate constants and V T (total distribution volume) which was used to measure longitudinal changes in the lesioned putamen. Sections for immunohistochemical labelling were prepared at the same time-points to evaluate correlations between in vivo [(18)F]DPA-714 binding and microglial/astrocytic activation. RESULTS: [(18)F]DPA-714 showed a widespread distribution with a higher signal in the thalamus and occipital cortex and lower binding in the cerebellum. TSPO was expressed throughout the whole brain and about 73 % of [(18)F]DPA-714 binding was specific for TSPO in vivo. The one-tissue compartment model (1-TCM) provided good and reproducible estimates of V T and rate constants, and V T values from the 1-TCM and the Logan approach were highly correlated (r (2) = 0.85). QA lesioning induced an increase in V T, which was +17 %, +54 %, +157 % and +39 % higher than baseline on days 7, 14, 21 and 91 after QA injection, respectively. Immunohistochemistry revealed an early microglial and a delayed astrocytic activation after QA injection. [(18)F]DPA-714 binding matched TSPO immunopositive areas and showed a stronger colocalization with CD68 microglia than with GFAP-activated astrocytes. CONCLUSION: [(18)F]DPA-714 binds to TSPO with high specificity in the primate brain under normal conditions and in the QA model. This tracer provides a sensitive tool for assessing neuroinflammation in the human brain.
Authors: Robert B Innis; Vincent J Cunningham; Jacques Delforge; Masahiro Fujita; Albert Gjedde; Roger N Gunn; James Holden; Sylvain Houle; Sung-Cheng Huang; Masanori Ichise; Hidehiro Iida; Hiroshi Ito; Yuichi Kimura; Robert A Koeppe; Gitte M Knudsen; Juhani Knuuti; Adriaan A Lammertsma; Marc Laruelle; Jean Logan; Ralph Paul Maguire; Mark A Mintun; Evan D Morris; Ramin Parsey; Julie C Price; Mark Slifstein; Vesna Sossi; Tetsuya Suhara; John R Votaw; Dean F Wong; Richard E Carson Journal: J Cereb Blood Flow Metab Date: 2007-05-09 Impact factor: 6.200
Authors: Jennifer M Coughlin; Yuchuan Wang; Shuangchao Ma; Chen Yue; Pearl K Kim; Ashley V Adams; Heidi V Roosa; Kenneth L Gage; Marigo Stathis; Rana Rais; Camilo Rojas; Jennifer L McGlothan; Crystal C Watkins; Ned Sacktor; Tomas R Guilarte; Yun Zhou; Akira Sawa; Barbara S Slusher; Brian Caffo; Michael Kassiou; Christopher J Endres; Martin G Pomper Journal: J Neurovirol Date: 2014-02-25 Impact factor: 2.643
Authors: J Logan; J S Fowler; N D Volkow; A P Wolf; S L Dewey; D J Schlyer; R R MacGregor; R Hitzemann; B Bendriem; S J Gatley Journal: J Cereb Blood Flow Metab Date: 1990-09 Impact factor: 6.200
Authors: R M Moresco; T Lavazza; S Belloli; M Lecchi; A Pezzola; S Todde; M Matarrese; A Carpinelli; E Turolla; V Zimarino; P Popoli; A Malgaroli; F Fazio Journal: Eur J Nucl Med Mol Imaging Date: 2007-12-15 Impact factor: 9.236
Authors: Cornelius K Donat; Khaled Gaber; Jürgen Meixensberger; Peter Brust; Lars H Pinborg; Henrik H Hansen; Jens D Mikkelsen Journal: Neuromolecular Med Date: 2016-03-11 Impact factor: 3.843
Authors: Bastian Zinnhardt; Michael Müther; Wolfgang Roll; Philipp Backhaus; Astrid Jeibmann; Claudia Foray; Cristina Barca; Christian Döring; Bertrand Tavitian; Frédéric Dollé; Matthias Weckesser; Alexandra Winkeler; Sven Hermann; Stefan Wagner; Heinz Wiendl; Walter Stummer; Andreas H Jacobs; Michael Schäfers; Oliver M Grauer Journal: Neuro Oncol Date: 2020-07-07 Impact factor: 12.300
Authors: Song Luo; Xiang Kong; Jin Rong Wu; Chun Yan Wang; Ying Tian; Gang Zheng; Yun Yan Su; Guang Ming Lu; Long Jiang Zhang; Gui Fen Yang Journal: Metab Brain Dis Date: 2018-07-02 Impact factor: 3.584
Authors: Donatienne Van Weehaeghe; Evelien Van Schoor; Joke De Vocht; Michel Koole; Bala Attili; Sofie Celen; Lieven Declercq; Dietmar R Thal; Philip Van Damme; Guy Bormans; Koen Van Laere Journal: J Nucl Med Date: 2019-09-27 Impact factor: 11.082
Authors: Xiang Kong; Song Luo; Jin Rong Wu; Shawn Wu; Carlo N De Cecco; U Joseph Schoepf; Adam J Spandorfer; Chun Yan Wang; Ying Tian; Hui Juan Chen; Guang Ming Lu; Gui Fen Yang; Long Jiang Zhang Journal: Theranostics Date: 2016-05-24 Impact factor: 11.556
Authors: Ina Israel; Andrea Ohsiek; Ehab Al-Momani; Christiane Albert-Weissenberger; Christian Stetter; Stine Mencl; Andreas K Buck; Christoph Kleinschnitz; Samuel Samnick; Anna-Leena Sirén Journal: J Neuroinflammation Date: 2016-06-07 Impact factor: 8.322
Authors: Sabrina Paganoni; Mohamad J Alshikho; Nicole R Zürcher; Paul Cernasov; Suma Babu; Marco L Loggia; James Chan; Daniel B Chonde; David Izquierdo Garcia; Ciprian Catana; Caterina Mainero; Bruce R Rosen; Merit E Cudkowicz; Jacob M Hooker; Nazem Atassi Journal: Neuroimage Clin Date: 2017-10-25 Impact factor: 4.881