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 smallanimal 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 wildtype mice of various ages were examined by small-animal PET. We acquired 90-min dynamic emission data with 18 F-GE180 for imaging activated microglia (18-kD translocator protein ligand [TSPO]) and static 30-to 60-min recordings with 18 F-FDG for energy metabolism and 18 F-florbetaben for amyloidosis. Optimal fusion of PET data was obtained through automatic nonlinear spatial normalization, and SUVRs were calculated. For the novel TSPO tracer 18 F-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 18 F-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, 18 F-GE180 SUVR was slightly elevated in PS2APP mice at 5 mo (19%; P , 0.01) and distinctly increased at 16 mo (125%; 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 5 0.85; P , 0.001) and likewise with metabolism (R 5 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.

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FET PET reliably distinguishes between post-therapeutic benign lesions and tumour recurrence after initial treatment of low- and high-grade gliomas.

Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by complex behaviour during REM sleep. The aetiology of this disorder is still unknown, but a recent study showed an association between RBD and Parkinson's disease. We therefore studied striatal postsynaptic dopamine D2 receptor density with [123I](S)-2-hydroxy-3-iodo-6-methoxy-(1-ethyl-2-pyrrolidinylmethyl ) benzamide ([123I]IBZM) and the striatal presynaptic dopamine transporter with (N)-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4-chlorop henyl) tropane ([123I]IPT) using single-photon emission computed tomography (SPECT) in patients with idiopathic RBD. We compared the [123I]IPT-SPECT results of five patients with polysomnographically confirmed idiopathic RBD with the [123I]IPT-SPECTs of seven age- and sex-matched controls without a history of sleep disorders, and of 14 patients with Parkinson's disease (Hoehn and Yahr stage I). All RBD patients had significantly reduced striatal [123I]IPT binding compared with the controls (RBD: right, 2.94 +/- 0.32, left, 3.03 +/- 0.41; controls: right, 4.41 +/- 0.17, left, 4.34 +/- 0.21; P = 0.003), but significantly higher striatal [123I]IPT binding compared with the striatum contralateral to the symptomatic body side of the Parkinson's disease patients (Parkinson's disease: ipsilateral, 3.17 +/- 0.36, P = 0.298; contralateral, 2.51 +/- 0.31, P = 0.019). Uptake of [123I]IBZM was not significantly different in the RBD group compared with the controls. This study demonstrates that [123I]IPT-SPECT is a useful diagnostic tool in RBD and that reduced striatal dopamine transporters may be a pathophysiological mechanism of idiopathic RBD. (Results are given as mean +/- standard deviation.)

FDG-PET shows that microglial activation might drive cerebral glucose uptake in mice and patients with AD.