scholarly journals How to Modulate Tumor Hypoxia for Preclinical In Vivo Imaging Research

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Sven De Bruycker ◽  
Christel Vangestel ◽  
Steven Staelens ◽  
Tim Van den Wyngaert ◽  
Sigrid Stroobants
Keyword(s):  
Tumor Hypoxia ◽  
Imaging Biomarkers ◽  
Tumor Aggressiveness ◽  
Poor Clinical Outcome ◽  
The Past ◽  
Positron Emission ◽  
Cancer Models ◽  
Imaging Research

Tumor hypoxia is related with tumor aggressiveness, chemo- and radiotherapy resistance, and thus a poor clinical outcome. Therefore, over the past decades, every effort has been made to develop strategies to battle the negative prognostic influence of tumor hypoxia. For appropriate patient selection and follow-up, noninvasive imaging biomarkers such as positron emission tomography (PET) radiolabeled ligands are unprecedentedly needed. Importantly, before being able to implement these new therapies and potential biomarkers into the clinical setting, preclinical in vivo validation in adequate animal models is indispensable. In this review, we provide an overview of the different attempts that have been made to create differential hypoxic in vivo cancer models with a particular focus on their applicability in PET imaging studies.

scholarly journals Imaging of microglial activation in MS using PET: Research use and potential future clinical application

2016 ◽  
Vol 23 (4) ◽  
pp. 496-504 ◽  
Author(s):  
Laura Airas ◽  
Eero Rissanen ◽  
Juha Rinne
Keyword(s):  
Complex Disease ◽  
Treatment Options ◽  
Quantitative Information ◽  
Imaging Biomarkers ◽  
In Vivo Evaluation ◽  
Non Invasive ◽  
Positron Emission ◽  
Magnetic Resonance Imaging Mri

Multiple sclerosis (MS) is a complex disease, where several processes can be selected as a target for positron emission topography (PET) imaging. Unlike magnetic resonance imaging (MRI), PET provides specific and quantitative information, and unlike neuropathology, it can be non-invasively applied to living patients, which enables longitudinal follow-up of the MS pathology. In the study of MS, PET can be useful for in vivo evaluation of specific pathological characteristics at various stages of the disease. Increased understanding of the progressive MS pathology will enhance the treatment options of this undertreated condition. The ultimate goal of developing and expanding PET in the study of MS is to have clinical non-invasive in vivo imaging biomarkers of neuroinflammation that will help to establish prognosis and accurately measure response to therapeutics. This topical review provides an overview of the promises and challenges of the use of PET in MS.

scholarly journals Imaging biomarkers in neurodegeneration: current and future practices

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Peter N. E. Young ◽  
Mar Estarellas ◽  
Emma Coomans ◽  
Meera Srikrishna ◽  
Helen Beaumont ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Imaging Biomarkers ◽  
New Techniques ◽  
Multimodal Analysis ◽  
The Past ◽  
Positron Emission ◽  
University College London ◽  
Magnetic Resonance Imaging Mri ◽  
The University

AbstractThere is an increasing role for biological markers (biomarkers) in the understanding and diagnosis of neurodegenerative disorders. The application of imaging biomarkers specifically for the in vivo investigation of neurodegenerative disorders has increased substantially over the past decades and continues to provide further benefits both to the diagnosis and understanding of these diseases. This review forms part of a series of articles which stem from the University College London/University of Gothenburg course “Biomarkers in neurodegenerative diseases”. In this review, we focus on neuroimaging, specifically positron emission tomography (PET) and magnetic resonance imaging (MRI), giving an overview of the current established practices clinically and in research as well as new techniques being developed. We will also discuss the use of machine learning (ML) techniques within these fields to provide additional insights to early diagnosis and multimodal analysis.

scholarly journals PET Metabolic Biomarkers for Cancer

2016 ◽  
Vol 8s2 ◽  
pp. BIC.S27483 ◽  
Author(s):  
Etienne Croteau ◽  
Jennifer M. Renaud ◽  
Marie Anne Richard ◽  
Terrence D. Ruddy ◽  
François Bénard ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ketone Bodies ◽  
Imaging Biomarkers ◽  
Substrate Consumption ◽  
Cancer Proliferation ◽  
Positron Emission ◽  
Pet Radiotracers ◽  
Metabolic Biomarkers

The body's main fuel sources are fats, carbohydrates (glucose), proteins, and ketone bodies. It is well known that an important hallmark of cancer cells is the overconsumption of glucose. Positron emission tomography (PET) imaging using the glucose analog 18F-fluorodeoxyglucose (18F-FDG) has been a powerful cancer diagnostic tool for many decades. Apart from surgery, chemotherapy and radiotherapy represent the two main domains for cancer therapy, targeting tumor proliferation, cell division, and DNA replication–-all processes that require a large amount of energy. Currently, in vivo clinical imaging of metabolism is performed almost exclusively using PET radiotracers that assess oxygen consumption and mechanisms of energy substrate consumption. This paper reviews the utility of PET imaging biomarkers for the detection of cancer proliferation, vascularization, metabolism, treatment response, and follow-up after radiation therapy, chemotherapy, and chemotherapy-related side effects.

scholarly journals News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 252
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Neurodegenerative Diseases ◽  
Imaging Techniques ◽  
Imaging Biomarkers ◽  
Positron Emission ◽  
Specific Proteins ◽  
Great Relevance ◽  
The Brain ◽  
Positive Point

Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.

scholarly journals Novel PET Biomarkers to Disentangle Molecular Pathways across Age-Related Neurodegenerative Diseases

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2581
Author(s):  
Heather Wilson ◽  
Marios Politis ◽  
Eugenii A. Rabiner ◽  
Lefkos T. Middleton
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Misfolding ◽  
Imaging Technique ◽  
Emission Tomography ◽  
Imaging Biomarkers ◽  
Synaptic Dysfunction ◽  
Molecular Pathways ◽  
Age Related ◽  
Positron Emission

There is a need to disentangle the etiological puzzle of age-related neurodegenerative diseases, whose clinical phenotypes arise from known, and as yet unknown, pathways that can act distinctly or in concert. Enhanced sub-phenotyping and the identification of in vivo biomarker-driven signature profiles could improve the stratification of patients into clinical trials and, potentially, help to drive the treatment landscape towards the precision medicine paradigm. The rapidly growing field of neuroimaging offers valuable tools to investigate disease pathophysiology and molecular pathways in humans, with the potential to capture the whole disease course starting from preclinical stages. Positron emission tomography (PET) combines the advantages of a versatile imaging technique with the ability to quantify, to nanomolar sensitivity, molecular targets in vivo. This review will discuss current research and available imaging biomarkers evaluating dysregulation of the main molecular pathways across age-related neurodegenerative diseases. The molecular pathways focused on in this review involve mitochondrial dysfunction and energy dysregulation; neuroinflammation; protein misfolding; aggregation and the concepts of pathobiology, synaptic dysfunction, neurotransmitter dysregulation and dysfunction of the glymphatic system. The use of PET imaging to dissect these molecular pathways and the potential to aid sub-phenotyping will be discussed, with a focus on novel PET biomarkers.

scholarly journals Imaging biomarkers for amyloid: a new generation of probes and what lies ahead

2014 ◽  
Vol 26 (5) ◽  
pp. 703-707 ◽  
Author(s):  
Antoine Leuzy ◽  
Eduardo Rigon Zimmer ◽  
Venkat Bhat ◽  
Pedro Rosa-Neto ◽  
Serge Gauthier
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Work Group ◽  
Imaging Biomarkers ◽  
Amyloid A ◽  
Positron Emission ◽  
Communicative Disorders ◽  
Physiologic Parameters ◽  
New Generation

Since the original 1984 criteria for Alzheimer's disease (AD), put forth by a work group jointly established by the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer's Disease and Related Disorders Association (ADRDA) (McKhann et al., 1984), important advances have occurred in our ability to detect AD pathophysiology, with the incorporation of biomarkers – defined as anatomic, biochemical, or physiologic parameters that provide in vivo evidence of AD neuropathology (Cummings, 2011) – that can improve the certainty of AD diagnosis. Use of imaging biomarkers such as positron emission tomography (PET) with amyloid ligands, particularly in asymptomatic and pre-dementia stages of AD, however, has been the subject of debate (Dubois et al., 2013), with arguments both for and against the biomarker driven diagnosis of AD.

scholarly journals A 3D View of Colorectal Cancer Models in Predicting Therapeutic Responses and Resistance

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 227
Author(s):  
Eileen Reidy ◽  
Niamh A. Leonard ◽  
Oliver Treacy ◽  
Aideen E. Ryan
Keyword(s):  
Colorectal Cancer ◽  
3D Model ◽  
Treatment Options ◽  
3D Models ◽  
In Vivo Studies ◽  
The Past ◽  
Monolayer Cultures ◽  
Cancer Models

Although there have been many advances in recent years for the treatment of colorectal cancer (CRC), it still remains the third most common cause of cancer-related deaths worldwide. Many patients with late stage CRC display resistance to multiple different therapeutics. An important aspect in developing effective therapeutics for CRC patients is understanding the interactions that take place in the tumor microenvironment (TME), as it has been shown to contribute to drug resistance in vivo. Much research over the past 100 years has focused on 2D monolayer cultures or in vivo studies, however, the efficacy in translating these to the clinic is very low. More recent studies are turning towards developing an effective 3D model of CRC that is clinically relevant, that can recapitulate the TME in vitro and bridge the gap between 2D cultures and in vivo studies, with the aim of reducing the use of animal models in the future. This review summarises the advantages and limitations of different 3D CRC models. It emphasizes how different 3D models may be optimised to study cellular and extracellular interactions that take place in the TME of CRC in an effort to allow the development of more translatable effective treatment options for patients.

scholarly journals Molecular and Cellular Complexity of Glioma. Focus on Tumour Microenvironment and the Use of Molecular and Imaging Biomarkers to Overcome Treatment Resistance

2020 ◽  
Vol 21 (16) ◽  
pp. 5631
Author(s):  
Silvia Valtorta ◽  
Daniela Salvatore ◽  
Paolo Rainone ◽  
Sara Belloli ◽  
Gloria Bertoli ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Treatment Resistance ◽  
Diagnostic Procedures ◽  
Cell Types ◽  
Therapy Resistance ◽  
Tumour Microenvironment ◽  
Imaging Biomarkers ◽  
Specific Gene ◽  
Positron Emission

This review highlights the importance and the complexity of tumour biology and microenvironment in the progression and therapy resistance of glioma. Specific gene mutations, the possible functions of several non-coding microRNAs and the intra-tumour and inter-tumour heterogeneity of cell types contribute to limit the efficacy of the actual therapeutic options. In this scenario, identification of molecular biomarkers of response and the use of multimodal in vivo imaging and in particular the Positron Emission Tomography (PET) based molecular approach, can help identifying glioma features and the modifications occurring during therapy at a regional level. Indeed, a better understanding of tumor heterogeneity and the development of diagnostic procedures can favor the identification of a cluster of patients for personalized medicine in order to improve the survival and their quality of life.

Functional PKC in vivo analysis using deficient mouse models

2007 ◽  
Vol 35 (5) ◽  
pp. 1018-1020 ◽  
Author(s):  
M. Leitges
Keyword(s):  
Expression Profiles ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
The Past ◽  
Kinase C ◽  
Pkc Isoforms ◽  
Pkc Protein Kinase C ◽  
In Vivo Analysis

The aim of our group is to identify PKC (protein kinase C) in vivo function by analysing individual PKC knockouts we have generated over the past few years. The general approach we are using to identify target tissues and/or defined cell populations within the mouse for further investigation is a detailed expression analysis of individual PKC isoforms. For these purposes, we have established several specific tools in the past that allow us to follow up isoform-specific PKC expression on a very precise level. Doing so, we have started to investigate PKC expression profiles under various tumour conditions in mice. As predicted, we were able to identify various PKC isoforms to be either up- or down-regulated during the development and progression of certain tumours, implying that these isoforms are substantially linked to the biology of these tumours. In order to prove this hypothesis, we then crossed relevant PKC knockout lines on the appropriate tumour background and analysed tumour growth and progression under PKC-deficient conditions. Exemplary of this approach, recent data generated with PKCα-deficient APCMin (adenomatous polyposis coli) mice identify PKCα in this system acting as a tumour suppressor instead of being a promoter as suggested from PMA data.

scholarly journals In Vivo Assessment of Drug Efficacy against Plasmodium falciparum Malaria: Duration of Follow-Up

2004 ◽  
Vol 48 (11) ◽  
pp. 4271-4280 ◽  
Author(s):  
Kasia Stepniewska ◽  
Walter R.J. Taylor ◽  
Mayfong Mayxay ◽  
Ric Price ◽  
Frank Smithuis ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Failure Rate ◽  
Drug Efficacy ◽  
Plasmodium Falciparum Malaria ◽  
Value Assessment ◽  
Randomized Controlled ◽  
The Past

ABSTRACT To determine the optimum duration of follow-up for the assessment of drug efficacy against Plasmodium falciparum malaria, 96 trial arms from randomized controlled trials (RCTs) with follow-up of 28 days or longer that were conducted between 1990 and 2003 were analyzed. These trials enrolled 13,772 patients, and participating patients comprised 23% of all patients enrolled in RCTs over the past 40 years; 61 (64%) trial arms were conducted in areas where the rate of malaria transmission was low, and 58 (50%) trial arms were supported by parasite genotyping to distinguish true recrudescences from reinfections. The median overall failure rate reported was 10% (range, 0 to 47%). The widely used day 14 assessment had a sensitivity of between 0 and 37% in identifying treatment failures and had no predictive value. Assessment at day 28 had a sensitivity of 66% overall (28 to 100% in individual trials) but could be used to predict the true failure rate if either parasite genotyping was performed (r 2 = 0.94) or if the entomological inoculation rate was known. In the assessment of drug efficacy against falciparum malaria, 28 days should be the minimum period of follow-up.

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