1,721,120 research outputs found
Doxorubicin effect on myocardial metabolism: a translational 18F-FDG PET/CT approach
No full textSystemic chemotherapy is the primary treatment for much diffuse solid neoplasms or hematological malignancies. One of its most significant drawbacks is the high incidence of side effects. Starting 30 years after treatment, the cumulative mortality from therapy-related medical illness exceeds the one from cancer recurrence. Besides secondary neoplasia, one of the most severe long-term complications is represented by cardiotoxicity that can significantly impact life expectancy, particularly in younger patients.
One of the most acknowledged models of cardiotoxicity is represented by doxorubicin (DXR)-induced cardiomyopathy. Despite an extensive research effort, the mechanisms underlying this dose-dependent complication have not been fully elucidated, although a significant role has been proposed for oxidative stress. Together with the late onset of heart failure symptoms, this relative uncertainty prevents the availability of reliable methods to predict the risk of developing contractile dysfunction. In this line, several studies reported that myocardial uptake of the glucose analog 18F-fluorodeoxyglucose (FDG) increases during and after DXR administration. Similarly, GLUT-1 and GLUT-4 expression have been found to increase in a dose-dependent fashion, in neonatal rat ventricular cells exposed to DXR. Altogether, these observations seem to suggest that DXR might increase myocardial glucose consumption. However, an accelerated glycolytic flux in left ventricular myocardium has been usually reported during ischemia as a result of the impairment in oxidative phosphorylation and the consequent increase in the NADH cytosol level. By contrast, the increased expression of
glucose carriers under DXR face a simultaneous evident oxidative damage to cardiomyocyte sarcolemma.
On the other hand, we recently documented that FDG uptake in cancer cells is relatively independent of overall glucose consumption and selectively tracks the activity of a glucose-processing machine located within the endoplasmic reticulum and triggered by the autosomic enzyme hexose-6P-dehydrogenase (H6PD). The potential interest of this pathway is related to the observation that H6PD silencing, besides reducing FDG uptake, also caused a profound fall in the crucial cofactor for redox control NADPH. Whether confirmed to non-cancer cells, this finding might imply that FDG is a marker of cell’s anti-oxidative stress competency.
Based on these considerations, the present Ph.D. project aimed to:
1. Characterize the direct redox and metabolic effect of Doxorubicin in cardiomyocytes.
2. Characterize the DXR cardiotoxic effect in experimental animals.
3. Characterize the DXR cardiotoxic impact on cancer patients.
Obtained results showed that FDG PET/CT might represent an early predictor of subsequent cardiotoxicity in cancer patients treated with DXR. Moreover, the application of PET/CT may also extend beyond the mere cardiotoxicity identification providing mechanistic insight on the cardiotoxic pathophysiology. Indeed, this tool further enriched the current knowledge on energy metabolism impairment in the DXR-induced cardiotoxic cascade
Reply: One Bite from the Apple, One Bite from the Orange in the PRECISE-MDT Study and Limitations of Retrospective Study Design and Potential Bias in the PRECISE-MDT Study
No full textImaging biomarkers in Alzheimer's disease: Added value in the clinical setting
No full textOver the last 20 years the availability of magnetic resonance imaging and positron-emission tomography technologies as well as of cerebrospinal fluid biomarkers has allowed research and clinical approach to Alzheimer's disease (AD) to move towards the earliest manifestations of the disease. This new approach resulted in an increasing knowledge about in-vivo biological and neuropathological processes of each phase of the AD-related damage from preclinical, to mild cognitive impairment, and finally to dementia due to AD. The present narrative review deals with the available data as well as with the unsolved issued related to the incorporation of AD biomarkers into the clinical practice. Ongoing research efforts aiming to better define and implement the use of imaging AD biomarkers in clinical practice according to a patient-centered approach and sustainability for clinical-care systems are also discussed
Amyloid PET Imaging: Standardization and Integration with Other Alzheimer’s Disease Biomarkers
No full textAmyloid plaques are a neuropathologic hallmark of Alzheimerâs disease (AD), which can be imaged through positron emission tomography (PET) technology using radiopharmaceuticals that selectively bind to the fibrillar aggregates of amyloid-Î2 plaques (Amy-PET). Several radiotracers for amyloid PET have been investigated, including11C-Pittsburgh compound B and the18F-labeled compounds such as18F-florbetaben,18F-florbetapir, and18F-flutemetamol. Besides the injected radiotracer, images can be interpreted by means of visual/qualitative, semiquantitative, and quantitative criteria. Here we summarize the main differences between the available radiotracers for Amy-PET, the proposed interpretation criteria, and analytical methods
Amyloid positron emission tomography and cognitive reserve
No full textAlzheimer's disease (AD) is characterized by a non-linear progressive course and several aspects influence the relationship between cerebral amount of AD pathology and the clinical expression of the disease. Brain cognitive reserve (CR) refers to the hypothesized capacity of an adult brain to cope with brain damage in order to minimize symptomatology. CR phenomenon contributed to explain the disjunction between the degree of neurodegeneration and the clinical phenotype of AD. The possibility to track brain amyloidosis (Aβ) in vivo has huge relevance for AD diagnosis and new therapeutic approaches. The clinical repercussions of positron emission tomography (PET)-assessed Aβ load are certainly mediated by CR thus potentially hampering the prognostic meaning of amyloid PET in selected groups of patients. Similarly, amyloid PET and cerebrospinal fluid amyloidosis biomarkers have recently provided new evidence for CR. The present review discusses the concept of CR in the framework of available neuroimaging studies and specifically deals with the reciprocal influences between amyloid PET and CR in AD patients and with the potential consequent interventional strategies for AD
18F-FDG-PET and MRI in autoimmune encephalitis: a systematic review of brain findings
No full textIn the diagnostic assessment of autoimmune encephalitis (AE) associated with antineural antibody (Ab) imaging with 18F-fluorodeoxyglucose (FDG), positron emission tomography (PET) was initially only used to screen for occult malignancies in paraneoplastic cases. Today accumulating evidence also supports the use of PET imaging for the objective assessment of metabolic changes in the brain of patients with AE. On the other hand, magnetic resonance imaging (MRI) of the brain reveals a variable picture depending on the specific syndrome and associated antibody, and may be normal in a sizable proportion of patients.From a systematic review of the literature, it seems that some specific metabolic patterns correlate with the presence of specific Ab, such as a cerebral posterior hypometabolism in anti-NMDAR encephalitis, and a mesiotemporal hypermetabolism (associated with hyperintensities and swollen structures on MRI T2) in encephalitis with LGI1 and onconeural Ab. To ascertain the prognostic value of FDG-PET and its role in driving therapy, larger (preferably longitudinal) studies are needed on age-matched, untreated patients with the same Ab status, who undergo imaging at a similar time after the onset of their symptoms. This would enable a systematic correlation between MRI and FDG-PET findings, and help to clarify a number of unsolved clinical and technical issues
Evaluation of response to immune checkpoint inhibitors: Is there a role for positron emission tomography?
Full text linkStrategies targeting intracellular negative regulators such as immune checkpoint inhibitors (ICPIs) have demonstrated significant antitumor activity across a wide range of solid tumors. In the clinical practice, the radiological effect of immunotherapeutic agents has raised several more relevant and complex challenges for the determination of their imaging-based response at single patient level. Accordingly, it has been suggested that the conventional Response Evaluation Criteria in Solid Tumors assessment alone, based on dimensional evaluation provided by computed tomography (CT), tends to underestimate the benefit of ICPIs at least in a subset of patients, supporting the need of immune-related response criteria. Different from CT, very few data are available for the evaluation of immunotherapy by means of18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, since the antineoplastic activity of ICPIs is highly related to the activation of T cells against cancer cells, FDG accumulation might cause false-positive findings. Yet, discrimination between benign and malignant processes represents a huge challenge for FDG-PET in this clinical setting. Consequently, it might be of high interest to test the complex and variegated response to ICPIs by means of PET and thus it is worthwhile to ask if a similar introduction of immune-related PET-based criteria could be proposed in the future. Finally, PET might offer a new insight into the biology and pathophysiology of ICPIs thanks to a growing number of non-invasive immune-diagnostic approaches based on non-FDG tracers
Alzheimer's disease (AD) co-pathology in dementia with Lewy bodies (DLB): implications in the disease modification era
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