Abstract
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Objectives To evaluate [18F]DPA-716 a new candidate radiotracer for TSPO 18 kDa, using an acute inflammatory rat model in comparison with two other pyrazolopyrimidines: [18F]DPA-714 and [11C]DPA-713.
Methods The AMPA rat model was used to study in vitro and in vivo specific and non-specific binding using autoradiography and µPET imaging on a Concorde Focus P220 PET camera.
Results Autoradiography demonstrated a high contrast in the lesion versus the contralateral side (p<0.001), with an ipsi-to-contralateral ratio of 4.8±1.1 that disappeared by adding an excess of PK11195 or non labeled DPA-716. The binding of [18F]DPA-716 was not affected by adding flumazenil. In vivo PET imaging showed a significantly increased uptake in the lesioned side as compared to the contralateral side, already 2 minutes after injection and up to 60 minutes (p<0.01). Displacement studies with PK11195 and non-labeled DPA-716 showed a rapid and complete displacement of [18F]DPA-716 binding from the lesion. Finally, modelisation of the PET data using the “simplified-reference-tissue-model” showed increased binding potential (BP) in comparison to the BP of [11C]PK11195 measured in the same model (2.0±0.4 versus 1.1±0.2)(Table 1).
Conclusions [18F]DPA-716 is a promising radiotracer for imaging acute neuroinflammation in rat. The properties of this new pyrazolopyrimidine are undoubtedly superior to those described for [11C]PK11195, but not to those recorded for [18F]DPA-714 and [11C]DPA-713.
Research Support Funded by the EU FP6 networks DiMI (LSHB-CT-2005-512146) EMIL(LSHC-CT-2004-503569), Canceropole IDF and Institut du Cancer