Comparison of high and low molar activity TSPO tracer [ 18 F]F-DPA in a mouse model of Alzheimer's disease.

Autor: Keller T; Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku and Turku University Central Hospital, Turku, Finland.; Department of Chemistry, University of Turku, Turku, Finland., López-Picón FR; MediCity Research Laboratory, University of Turku, Turku, Finland.; PET Preclinical Imaging Laboratory, Turku PET Centre, University of Turku, Turku, Finland., Krzyczmonik A; Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku and Turku University Central Hospital, Turku, Finland.; Department of Chemistry, University of Turku, Turku, Finland., Forsback S; Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku and Turku University Central Hospital, Turku, Finland.; Department of Chemistry, University of Turku, Turku, Finland., Takkinen JS; MediCity Research Laboratory, University of Turku, Turku, Finland.; PET Preclinical Imaging Laboratory, Turku PET Centre, University of Turku, Turku, Finland., Rajander J; Accelerator Laboratory, Turku PET Centre, Åbo Akademi University, Turku, Finland., Teperi S; Department of Biostatistics, University of Turku, Turku, Finland., Dollé F; CEA, I2BM, Service Hospitalier Frédéric Joliot, Orsay, France., Rinne JO; Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku and Turku University Central Hospital, Turku, Finland., Haaparanta-Solin M; MediCity Research Laboratory, University of Turku, Turku, Finland.; PET Preclinical Imaging Laboratory, Turku PET Centre, University of Turku, Turku, Finland., Solin O; Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku and Turku University Central Hospital, Turku, Finland.; Department of Chemistry, University of Turku, Turku, Finland.; Accelerator Laboratory, Turku PET Centre, Åbo Akademi University, Turku, Finland.
Jazyk: angličtina
Zdroj: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2020 May; Vol. 40 (5), pp. 1012-1020. Date of Electronic Publication: 2019 May 29.
DOI: 10.1177/0271678X19853117
Abstrakt: [ 18 F]F-DPA, a novel translocator protein 18 kDa (TSPO)-specific radioligand for imaging neuroinflammation, has to date been synthesized with low to moderate molar activities (A m 's). In certain cases, low A m can skew the estimation of specific binding. The high proportion of the non-radioactive component can reduce the apparent-specific binding by competitively binding to receptors. We developed a nucleophilic synthesis of [ 18 F]F-DPA resulting in high A m (990 ± 150 GBq/µmol) and performed in vivo comparison with low A m (9.0 ± 2.9 GBq/µmol) [ 18 F]F-DPA in the same APP/PS1-21 and wild-type mice (injected masses: 0.34 ± 0.13 µg/kg and 38 ± 15 µg/kg, respectively). The high level of microgliosis in the APP/PS1-21 mouse model enables good differentiation between diseased and healthy animals and serves better to distinguish the effect of differing A m on specific binding. The differing injected masses affect the washout profile and shape of the time-activity curves. Ratios of standardized uptake values obtained with high and low A m [ 18 F]F-DPA demonstrate that there is a 1.5-fold higher uptake of radioactivity in the brains of APP/PS1-21 animals when imaging is carried out with high A m [ 18 F]F-DPA. The differences between APP/PS1-21 and wild-type animals showed higher significance when high A m was used.
Databáze: MEDLINE
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