Mapping Pathological &lt;sup&gt;99m&lt;/sup&gt;Tc-&lt;i&gt;d,l&lt;/i&gt;-Hexamethylpropylene Amine Oxime Uptake in Alzheimer’s Disease and Frontal Lobe Dementia with SPECT

Pagani, Marco; Salmaso, Dario; Ramström, Christina; Jonsson, Cathrine; Lundqvist, Roger; Thurfjell, Lennart; Schnell, Per-Olof; Wagner, Annemarie; Jacobsson, Hans; Larsson, Stig

doi:10.1159/000051255

Cited by 17 publications

(8 citation statements)

References 28 publications

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“…Although it is established that CSA modulates Rho123 transport by ABCB1, there are some conflicting results in the literature about the secretion of Rho123 by the kidney and the effects of CSA in this secretion [17, 18, 19, 22, 33, 34]. The classical assay used to observe modulation of MDR phenotype in cells in culture involves the measurement of cellular accumulation of fluorescent dyes in the presence or absence of a given modulator [16].…”

Section: Resultsmentioning

confidence: 99%

“…Although Rho123 is not a chemotherapeutic, it has been widely used in studies of ABCB1-mediated transport in the kidney and other organs, due to its fluorescent properties and transport characteristics [16, 17, 18, 19, 21, 33, 34]. In the present study, we used Rho123 as a model to investigate the effects of CSA in cellular accumulation of drugs, using different experimental protocols.…”

Section: Discussionmentioning

confidence: 99%

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Comparative Study on the Effects of Cyclosporin A in Renal Cells in Culture

Nascimento

Braga

Capella

et al. 2005

Nephron Exp Nephrol

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Background: Although cyclosporin A (CSA) inhibits P-glycoprotein (ABCB1), the relationship between this inhibition and CSA-induced nephrotoxicity is not established. Methods: Three renal cell lines were used to investigate the effects of CSA in cellular viability and accumulation of rhodamine 123 (Rho123): LLC-PK1, which does not express ABCB1 substantially; MDCK, expressing moderate amounts of this protein, and Ma104 cells, which express high amounts of ABCB1. Results: The viability was significantly reduced in the three cell lines after treatment with CSA concentrations >10 µM. Ma104 was the more resistant and LLC-PK1 the more sensitive. CSA increased Rho123 accumulation in the three cell lines when incubated simultaneously, MDCK presenting the higher increase. However, different results were achieved when the periods of incubation with Rho123 and CSA were disconnected: a post-incubation with CSA was more effective in Ma104 cells, while MDCK and LLC-PK1 showed no difference between pre-, co- and post-incubation with CSA. Conclusions: Our results suggest that the effects of CSA may be divided into two groups: ABCB1-independent (direct injury), and ABCB1-dependent toxicity, due to modulation of its activity. This could result in increased accumulation of noxious ABCB1 substrates, contributing to CSA-induced nephrotoxicity. Furthermore, the mechanisms of ABCB1 modulation by CSA may be different for different cell lines.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparative Study on the Effects of Cyclosporin A in Renal Cells in Culture

Nascimento

Braga

Capella

et al. 2005

Nephron Exp Nephrol

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“…The SPM approach has never been applied to directly compare FTD and AD patients. Only one study has proposed the use of 99m Tc-HMPAO SPET images anatomically normalised into a standard space (computerised brain atlas) in order to improve the detection of rCBF differences between two groups of patients with FTD and AD [27]. In that study, however, only regions more affected in FTD than in AD were visualised and no voxel-by-voxel statistical analysis was performed.…”

Section: Discussionmentioning

confidence: 99%

“…We did not use the occipital cortex since tracer uptake in this region can be affected by environmental factors at the time of injection [16]. We also excluded subcortical structures, such as basal ganglia, that have been shown to be involved in AD and FTD [7,27]. Finally, it was unclear whether the cerebellum could be used as a valid reference region for the comparison of FTD and AD.…”

Section: Methodological Considerationsmentioning

confidence: 99%

Voxel-based comparison of rCBF SPET images in frontotemporal dementia and Alzheimer's disease highlights the involvement of different cortical networks

Varrone

Pappatà

Caracò³

et al. 2002

European Journal of Nuclear Medicine and Molecular Imaging

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Characteristic patterns of regional cerebral blood flow (rCBF) reduction, as detected by technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) single-photon emission tomography (SPET), may help clinicians in differentiating patients with frontotemporal dementia (FTD) from those with Alzheimer's disease (AD). However, in some cases these patients may share common rCBF abnormalities and the visual analysis and/or the region of interest (ROI) approach may not sensitively detect more localised focal changes that could be more specific for each pathology. Recently, automated voxel-by-voxel statistical analysis of perfusion brain maps has been applied to SPET images. This method has the advantage of including the rCBF information for the whole brain for statistical analysis without any a priori hypothesis regarding the regions possibly involved. This could result in a better characterisation of rCBF differences in brain regions while also reducing the operator's subjectivity and the time required for data analysis. The purpose of this study was to apply such a technique to highlight the specific brain areas showing a relative functional involvement in FTD and AD. Thus, we compared the relative rCBF patterns obtained in eight FTD patients with those obtained in 21 AD patients using (99m)Tc-HMPAO SPET and statistical parametric mapping (SPM). When FTD patients were compared with AD patients, relatively lower rCBF was observed in right medial frontal cortex (BA 8, 9, 10), right anterior cingulate cortex (BA 32), right temporal cortex (BA 21/22), right orbitofrontal cortex (BA 11) and ventrolateral prefrontal cortex (BA 47); in BA 47 the reduction was evident bilaterally but was more marked on the right side. On the other hand, when AD patients were compared with FTD patients, a significant relative rCBF decrease was found in the bilateral superior parietal cortex (BA 7); this decrease was more extensive on the left side, where it also included the inferior parietal (BA 40), superior occipital (BA 19) and temporo-occipital regions (BA 39, 19). The results of this study confirm the preferential involvement of the frontotemporal regions in FTD patients and of the temporoparietal regions in AD patients. Furthermore, they highlight the networks that are more specifically impaired in these disorders and that could be implicated in the emotional-behavioural and cognitive disturbances that characterise FTD and AD respectively.

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“…99m Tc-HMPAO SPECT is useful to differentiate CBD from other alternative diseases, because in CBD significant reduction of radiopharmaceutical uptake is in frontal, parietal, temporal cortices of the more affected side, in the thalamus and in pontocerebellar regions [30][31][32]34]. In vascular dementias, hypoperfusion is confirmed in bilateral thalami, the anterior cingulate gyrus, the temporal gyri, the caudate heads and the left parahippocampal gyrus, suggesting functional disconnection between frontal lobes and subcortical structures [31].…”

Section: Discussionmentioning

confidence: 99%

Could a structural damage mimic a Parkinson plus syndrome?

Alexoudi

Zalonis²,

Stathis³

2013

Open Medicine

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AbstractCorticobasal syndrome (CBS) is a progressive disease that includes a heterogeneous neuropathological spectrum. In the majority of cases, corticobasal degeneration (CBD) is the underlying disease. Clinical heterogeneity is reflected in the clinical presentation of the syndrome and consequently misdiagnosis is common. Our case is of interest because the symptoms, the poor response to L-dopa and the I123 Ioflupane CIT SPECT (DAT-SCAN) results were typical for CBD. However, the magnetic resonance imaging appearance suggested the possibility of a disease of vascular etiology. A 63-year-old woman presented in our outpatient clinic with symptoms of progressive clumsiness in the right arm when performing movements demanding fine motor skills, and mild speech difficulties. The brain magnetic resonance imaging (MRI) report described ischemic lesions in the left subcortical parietal areas, in the centrum semiovale, in periventricular white matter, cingulated gyrus bilaterally and moderate ventricle dilatation. A comprehensive neuropsychological study suggested mixed cortical and subcortical involvement. A DAT-SCAN examination showed a diminished dopamine transporter uptake in the left lenticular nucleus, suggesting parkinsonisn. For this patient, CBS-CBD was the most probable diagnosis, whereas vascular CBS was not excluded. This case report illustrates the low diagnostic sensitivity in predicting CBD and the overlap with other related neurodegenerative diseases. Finally, it demonstrates that in CBS, different underlying pathologies can be found at the same individual.

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Mapping Pathological <sup>99m</sup>Tc-<i>d,l</i>-Hexamethylpropylene Amine Oxime Uptake in Alzheimer’s Disease and Frontal Lobe Dementia with SPECT

Cited by 17 publications

References 28 publications

Comparative Study on the Effects of Cyclosporin A in Renal Cells in Culture

Comparative Study on the Effects of Cyclosporin A in Renal Cells in Culture

Voxel-based comparison of rCBF SPET images in frontotemporal dementia and Alzheimer's disease highlights the involvement of different cortical networks

Could a structural damage mimic a Parkinson plus syndrome?

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