florbetapir-f-18 and Disease-Models--Animal

The observation that amyloid radiotracers developed for Alzheimer's disease bind to cerebral white matter paved the road to nuclear imaging of myelin in multiple sclerosis. The lysolecithin (lysophosphatidylcholine (LPC)) rat model of demyelination proved useful in evaluating and comparing candidate radiotracers to target myelin. Focal demyelination following stereotaxic LPC injection is larger than lesions observed in experimental autoimmune encephalitis models and is followed by spontaneous progressive remyelination. Moreover, the contralateral hemisphere may serve as an internal control in a given animal. However, demyelination can be accompanied by concurrent focal necrosis and/or adjacent ventricle dilation. The influence of these side effects on imaging findings has never been carefully assessed. The present study describes an optimization of the LPC model and highlights the use of MRI for controlling the variability and pitfalls of the model. The prototypical amyloid radiotracer [

Topics: Aniline Compounds; Animals; Autoradiography; Brain Edema; Carbon Radioisotopes; Cerebral Ventricles; Corpus Callosum; Corpus Striatum; Demyelinating Diseases; Dilatation, Pathologic; Disease Models, Animal; Ethylene Glycols; False Positive Reactions; Fluorine Radioisotopes; Image Processing, Computer-Assisted; Injections; Lysophosphatidylcholines; Magnetic Resonance Imaging; Male; Multiple Sclerosis; Myelin Sheath; Neuroimaging; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Stereotaxic Techniques; Thiazoles

We aimed to monitor the timing of amyloid-β deposition in relation to changes in brain function using in vivo imaging with [18F]-AV45 and [18F]-FDG in a mouse model of Alzheimer's disease. TASTPM transgenic mice and wild-type controls were scanned longitudinally with [18F]-AV45 and [18F]-FDG before (3 months of age) and at multiple time points after the onset of amyloid deposition (6, 9, 12, and 15 months of age). As expected with increasing amyloidosis, TASTPM mice demonstrated progressive age-dependent increases in [18F]-AV45 uptake that were significantly higher than for WT from 9 months onwards and correlated to ex vivo measures of amyloid burden. The metabolism of [18F]-AV45 produces several brain penetrant radiometabolites and normalization to a reference region helps to negate this non-specific binding and improve the sensitivity of [18F]-AV45. The observed trajectory of [18F]-FDG alterations deviated from our proposed hypothesis of gradual decreases with worsening amyloidosis. While [18F]-FDG uptake in TASTPM mice was significantly lower than that of WT at 9 months, reduced [18F]-FDG was not associated with aging in TASTPM mice. Moreover, [18F]-FDG uptake did not correlate to measures of ex vivo amyloid burden. Our findings suggest that while amyloid-β is sufficient to induce hypometabolism, these pathologies are not linked in a dose-dependent manner in TASTPM mice.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Aniline Compounds; Animals; Brain; Disease Models, Animal; Ethylene Glycols; Fluorodeoxyglucose F18; Humans; Longitudinal Studies; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Positron-Emission Tomography; Presenilin-1; Time Factors