PT - JOURNAL ARTICLE AU - Matthias Brendel AU - Federico Probst AU - Anna Jaworska AU - Felix Overhoff AU - Viktoria Korzhova AU - Nathalie L. Albert AU - Roswitha Beck AU - Simon Lindner AU - Franz-Josef Gildehaus AU - Karlheinz Baumann AU - Peter Bartenstein AU - Gernot Kleinberger AU - Christian Haass AU - Jochen Herms AU - Axel Rominger TI - Glial Activation and Glucose Metabolism in a Transgenic Amyloid Mouse Model: A Triple-Tracer PET Study AID - 10.2967/jnumed.115.167858 DP - 2016 Jun 01 TA - Journal of Nuclear Medicine PG - 954--960 VI - 57 IP - 6 4099 - http://jnm.snmjournals.org/content/57/6/954.short 4100 - http://jnm.snmjournals.org/content/57/6/954.full SO - J Nucl Med2016 Jun 01; 57 AB - Amyloid imaging by small-animal PET in models of Alzheimer disease (AD) offers the possibility to track amyloidogenesis and brain energy metabolism. Because microglial activation is thought to contribute to AD pathology, we undertook a triple-tracer small-animal PET study to assess microglial activation and glucose metabolism in association with amyloid plaque load in a transgenic AD mouse model. Methods: Groups of PS2APP and C57BL/6 wild-type mice of various ages were examined by small-animal PET. We acquired 90-min dynamic emission data with 18F-GE180 for imaging activated microglia (18-kD translocator protein ligand [TSPO]) and static 30- to 60-min recordings with 18F-FDG for energy metabolism and 18F-florbetaben for amyloidosis. Optimal fusion of PET data was obtained through automatic nonlinear spatial normalization, and SUVRs were calculated. For the novel TSPO tracer 18F-GE180, we then calculated distribution volume ratios after establishing a suitable reference region. Immunohistochemical analyses with TSPO antisera, methoxy-X04 staining for fibrillary β-amyloid, and ex vivo autoradiography served as terminal gold standard assessments. Results: SUVR at 60–90 min after injection gave robust quantitation of 18F-GE180, which correlated well with distribution volume ratios calculated from the entire recording and using a white matter reference region. Relative to age-matched wild-type, 18F-GE180 SUVR was slightly elevated in PS2APP mice at 5 mo (+9%; P < 0.01) and distinctly increased at 16 mo (+25%; P < 0.001). Over this age range, there was a high positive correlation between small-animal PET findings of microglial activation with amyloid load (R = 0.85; P < 0.001) and likewise with metabolism (R = 0.61; P < 0.005). Immunohistochemical and autoradiographic findings confirmed the in vivo small-animal PET data. Conclusion: In this first triple-tracer small-animal PET in a well-established AD mouse model, we found evidence for age-dependent microglial activation. This activation, correlating positively with the amyloid load, implies a relationship between amyloidosis and inflammation in the PS2APP AD mouse model.