RT Journal Article
SR Electronic
T1 Glial Activation and Glucose Metabolism in a Transgenic Amyloid Mouse Model: A Triple-Tracer PET Study
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 954
OP 960
DO 10.2967/jnumed.115.167858
VO 57
IS 6
A1 Matthias Brendel
A1 Federico Probst
A1 Anna Jaworska
A1 Felix Overhoff
A1 Viktoria Korzhova
A1 Nathalie L. Albert
A1 Roswitha Beck
A1 Simon Lindner
A1 Franz-Josef Gildehaus
A1 Karlheinz Baumann
A1 Peter Bartenstein
A1 Gernot Kleinberger
A1 Christian Haass
A1 Jochen Herms
A1 Axel Rominger
YR 2016
UL http://jnm.snmjournals.org/content/57/6/954.abstract
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.