Clinical and Translational Imaging 

About: Clinical and Translational Imaging is an academic journal published by Springer Science+Business Media. The journal publishes majorly in the area(s): Medicine & Positron emission tomography. It has an ISSN identifier of 2281-5872. Over the lifetime, 547 publications have been published receiving 5389 citations.

Glucose metabolism in normal aging and Alzheimer's disease: Methodological and physiological considerations for PET studies.

Abstract: Alzheimer’s disease (AD) is an age-dependent neurodegenerative disorder associated with progressive loss of cognitive function. 2-[18F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) has long been used to measure resting-state cerebral metabolic rates of glucose, a proxy for neuronal activity. Several FDG PET studies have shown that metabolic reductions occur decades before onset of AD symptoms, suggesting that metabolic deficits may be an upstream event in at least some late-onset AD cases. This review explores this possibility, initially discussing the link between AD pathology, neurodegeneration, oxidative stress, and AD, and then discussing findings of FDG PET hypometabolism in AD patients as well as in at-risk individuals, especially those with a first-degree family history of late-onset AD. While the rare early-onset form of AD is due to autosomal dominant genetic mutations, the etiology and pathophysiology of age-dependent, late-onset AD is more complex. Recent FDG PET studies have shown that adult children of AD-affected mothers are more likely than those with AD-fathers to show AD-like brain changes. Given the connection between glucose metabolism and mitochondria, and the fact that mitochondrial DNA is maternally inherited in humans, it is here argued that altered bioenergetics may be an upstream event in those with a maternal history of late-onset AD. Biomarkers of AD have great potential for identifying AD endophenotypes in at-risk individuals, which may help direct investigation of potential susceptibility genes.

The development and validation of tau PET tracers: current status and future directions.

Abstract: To provide an overview on positron emission tomography (PET) imaging of tau pathology in Alzheimer’s disease (AD) and other neurodegenerative disorders. Different classes of tau tracers such as flortaucipir, THK5317, and PBB3 have been developed and utilized in previous clinical studies. In AD, the topographical distribution of tracer binding follows the known distribution of neurofibrillary tangles and is closely associated with neurodegeneration as well as the clinical phenotype of dementia. Significant retention of tracers has also been observed in the frequent site of the 4-repeat (4R) tau isoform deposits in non-AD tauopathies, such as in progressive supranuclear palsy. However, in vitro binding studies indicate that most tau tracers are less sensitive to straight tau filaments, in contrast to their high binding affinity to paired helical filaments of tau (PHF-tau). The first-generation of tau tracers shows off-target binding in the basal ganglia, midbrain, thalamus, choroid plexus, and venous sinus. Off-target binding of THK5351 to monoamine oxidase B (MAO-B) has been observed in disease-associated brain regions linked to neurodegeneration and is associated with astrogliosis in areas of misfolded protein accumulation. The second generation of tau tracers, such as [18F]MK-6240, is highly selective to PHF-tau with little off-target binding and have enabled the reliable assessment of PHF-tau burden in aging and AD. Tau PET tracers have enabled in vivo quantification of PHF-tau burden in human brains. Tau PET can help in understanding the underlying cause of dementia symptoms, and in patient selection for clinical trials of anti-dementia therapies.

Beta-amyloid imaging with florbetaben

Abstract: Florbetaben is a fluorine-18 (18F)-labeled stilbene derivative that was developed as a positron emission tomography (PET) tracer for routine clinical application to visualize β-amyloid plaques in the Alzheimer’s disease (AD) brain. The tracer successfully completed a global multicenter phase 0–III development program and was, as a consequence, recently approved by the US Food and Drug Administration and the European Medicines Agency. This review provides an overview on the florbetaben tracer characteristics and preclinical data leading to its human testing. Further, the favorable results of human pharmacokinetics, safety, and dosimetry evaluation of florbetaben are presented. Next, the results of the clinical testing of florbetaben are discussed, in which the tracer was shown to sensitively and specifically detect β-amyloid neuritic plaques, as evidenced by employing different gold standards (from clinical diagnosis to post mortem histopathology). The potential of florbetaben to predict AD dementia in cases of mild cognitive impairment and to assist in the differential diagnosis in cases of dementia is also described. Finally, potential clinical impact and clinical routine PET image acquisition and analysis protocols for florbetaben are discussed. Taken together, the evidence shows that florbetaben is a valuable β-amyloid-targeting PET tracer in the clinic with great potential to serve as a biomarker supporting clinical AD diagnosis.

Molecular mechanisms of hypoxia in cancer.

Abstract: Hypoxia is a condition of insufficient oxygen to support metabolism which occurs when the vascular supply is interrupted, or when a tumour outgrows its vascular supply. It is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. This review provides an overview of hypoxia imaging with Positron emission tomography (PET), with an emphasis on the biological relevance, mechanism of action, highlighting advantages, and limitations of the currently available hypoxia radiotracers. A comprehensive PubMed literature search was performed, identifying articles relating to biological significance and measurement of hypoxia, MRI methods, and PET imaging of hypoxia in preclinical and clinical settings, up to December 2016. A variety of approaches have been explored over the years for detecting and monitoring changes in tumour hypoxia, including regional measurements with oxygen electrodes placed under CT guidance, MRI methods that measure either oxygenation or lactate production consequent to hypoxia, different nuclear medicine approaches that utilise imaging agents the accumulation of which is inversely related to oxygen tension, and optical methods. The advantages and disadvantages of these approaches are reviewed, along with individual strategies for validating different imaging methods. PET is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. Even though hypoxia could have significant prognostic and predictive value in the clinic, the best method for hypoxia assessment has in our opinion not been realised.

Radiomics in PET: principles and applications

Abstract: Radiomics is an evolving field in which the extraction of large amounts of features from diagnostic medical images may be used to predict underlying molecular and genetic characteristics, thereby improving treatment response prediction and prognostication and potentially allowing personalisation of cancer treatment. There is increasing interest in extracting additional data from PET images, particularly novel features that describe the heterogeneity of voxel intensities, but a number of potential limitations need to be recognised and overcome. Nevertheless, some early data suggest that extraction of additional quantitative data may offer further predictive and prognostic information in individual patients.