Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 40, Issue 5, Pages 1012-1020Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X19853117
Keywords
APP; PS1-21; fluorine-18; Neuroinflammation; positron emission tomography; TSPO
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[F-18]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 [F-18]F-DPA resulting in high A(m) (990 +/- 150 GBq/mu mol) and performed in vivo comparison with low A(m) (9.0 +/- 2.9 GBq/mu mol) [F-18]F-DPA in the same APP/PS1-21 and wild-type mice (injected masses: 0.34 +/- 0.13 mu g/kg and 38 +/- 15 mu g/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) [F-18]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) [F-18]F-DPA. The differences between APP/PS1-21 and wild-type animals showed higher significance when high A(m) was used.
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