scholarly journals Noninvasive Assessment of Exosome Pharmacokinetics In Vivo: A Review

Pharmaceutics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 649 ◽  
Author(s):  
Do Hee Kim ◽  
Vinoth Kumar Kothandan ◽  
Hye Won Kim ◽  
Ki Seung Kim ◽  
Ji Young Kim ◽  
...  
Keyword(s):  
Lipid Membranes ◽  
Biological Fluid ◽  
Imaging Techniques ◽  
Tissue Samples ◽  
Positron Emission ◽  
Donor Cells ◽  
Therapy And Diagnosis ◽  
Analytical Standards ◽  
Original Donor

Exosomes, intraluminal vesicles that contain informative DNA, RNA, proteins, and lipid membranes derived from the original donor cells, have recently been introduced to therapy and diagnosis. With their emergence as an alternative to cell therapy and having undergone clinical trials, proper analytical standards for evaluating their pharmacokinetics must now be established. Molecular imaging techniques such as fluorescence imaging, magnetic resonance imaging, and positron emission tomography (PET) are helpful to visualizing the absorption, distribution, metabolism, and excretion of exosomes. After exosomes labelled with a fluorescer or radioisotope are administered in vivo, they are differentially distributed according to the characteristics of each tissue or lesion, and real-time biodistribution of exosomes can be noninvasively monitored. Quantitative analysis of exosome concentration in biological fluid or tissue samples is also needed for the clinical application and industrialization of exosomes. In this review, we will discuss recent pharmacokinetic applications to exosomes, including labelling methods for in vivo imaging and analytical methods for quantifying exosomes, which will be helpful for evaluating pharmacokinetics of exosomes and improving exosome development and therapy.

scholarly journals In Vivo Imaging of Biodegradable Implants and Related Tissue Biomarkers

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2348
Author(s):  
Leon Riehakainen ◽  
Chiara Cavallini ◽  
Paolo Armanetti ◽  
Daniele Panetta ◽  
Davide Caramella ◽  
...  
Keyword(s):  
Imaging Modality ◽  
Imaging Techniques ◽  
Special Focus ◽  
Tissue Remodelling ◽  
Biodegradable Implant ◽  
Advantages And Disadvantages ◽  
Non Invasive ◽  
Positron Emission ◽  
Longitudinal Imaging

Non-invasive longitudinal imaging of osseointegration of bone implants is essential to ensure a comprehensive, physical and biochemical understanding of the processes related to a successful implant integration and its long-term clinical outcome. This study critically reviews the present imaging techniques that may play a role to assess the initial stability, bone quality and quantity, associated tissue remodelling dependent on implanted material, implantation site (surrounding tissues and placement depth), and biomarkers that may be targeted. An updated list of biodegradable implant materials that have been reported in the literature, from metal, polymer and ceramic categories, is provided with reference to the use of specific imaging modalities (computed tomography, positron emission tomography, ultrasound, photoacoustic and magnetic resonance imaging) suitable for longitudinal and non-invasive imaging in humans. The advantages and disadvantages of the single imaging modality are discussed with a special focus on preclinical imaging for biodegradable implant research. Indeed, the investigation of a new implant commonly requires histological examination, which is invasive and does not allow longitudinal studies, thus requiring a large number of animals for preclinical testing. For this reason, an update of the multimodal and multi-parametric imaging capabilities will be here presented with a specific focus on modern biomaterial research.

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 Neurological update: neuroimaging in dementia

2020 ◽  
Vol 267 (11) ◽  
pp. 3429-3435
Author(s):  
Timothy Rittman
Keyword(s):  
Artificial Intelligence ◽  
Positron Emission Tomography ◽  
Clinical Practice ◽  
Imaging Techniques ◽  
Emission Tomography ◽  
Structural Imaging ◽  
Regulatory Issues ◽  
Positron Emission ◽  
Remarkable Progress

Abstract Neuroimaging for dementia has made remarkable progress in recent years, shedding light on diagnostic subtypes of dementia, predicting prognosis and monitoring pathology. This review covers some updates in the understanding of dementia using structural imaging, positron emission tomography (PET), structural and functional connectivity, and using big data and artificial intelligence. Progress with neuroimaging methods allows neuropathology to be examined in vivo, providing a suite of biomarkers for understanding neurodegeneration and for application in clinical trials. In addition, we highlight quantitative susceptibility imaging as an exciting new technique that may prove to be a sensitive biomarker for a range of neurodegenerative diseases. There are challenges in translating novel imaging techniques to clinical practice, particularly in developing standard methodologies and overcoming regulatory issues. It is likely that clinicians will need to lead the way if these obstacles are to be overcome. Continued efforts applying neuroimaging to understand mechanisms of neurodegeneration and translating them to clinical practice will complete a revolution in neuroimaging.

scholarly journals Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64–labeled daratumumab

2020 ◽  
Vol 4 (20) ◽  
pp. 5194-5202
Author(s):  
Amrita Krishnan ◽  
Vikram Adhikarla ◽  
Erasmus K. Poku ◽  
Joycelynne Palmer ◽  
Ammar Chaudhry ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Sensitivity And Specificity ◽  
Imaging Techniques ◽  
Phase 1 ◽  
Whole Body ◽  
Human Antibody ◽  
Whole Body Imaging ◽  
Positron Emission ◽  
Pet Ct

Abstract 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and nonmalignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with 64Cu via the chelator DOTA (64Cu-daratumumab), led to improved sensitivity and specificity over that of FDG. Here, we report the results of a phase 1 trial designed to (1) assess the safety and feasibility of 64Cu-daratumumab PET/CT and (2) preliminarily evaluate and characterize the ability of 64Cu-daratumumab to accurately detect or exclude MM lesions. A total of 12 daratumumab-naive patients were imaged. Prior to the injection of 15 mCi/5 mg of 64Cu-daratumumab, patients were treated with 0 (n = 3), 10 (n = 3), 45 (n = 3), or 95 mg (n = 3) of unlabeled daratumumab to assess its effect on image quality. No significant adverse events were observed from either unlabeled daratumumab or 64Cu-daratumumab. Of the dose levels tested, 45 mg unlabeled daratumumab was the most optimal in terms of removing background signal without saturating target sites. 64Cu-daratumumab PET/CT provided safe whole-body imaging of MM. A trial comparing the sensitivity and specificity of 64Cu-daratumumab PET/CT with that of FDG PET/CT is planned. This trial was registered at www.clinicaltrials.gov as #NCT03311828.

Opioids and brain imaging

2006 ◽  
Vol 2 (3) ◽  
pp. 147 ◽  
Author(s):  
Shyam Balasubramanian, MBBS, MD, FRCA ◽  
Patricia Morley-Forster, MD, FRCPC ◽  
Yves Bureau, PhD
Keyword(s):  
Imaging Techniques ◽  
Analgesic Efficacy ◽  
New Drugs ◽  
Opioidergic System ◽  
Central Processing ◽  
Gate Control Theory ◽  
Positron Emission ◽  
Gate Control ◽  
Chronic Pain Conditions

Since the introduction of the gate-control theory, a plethora of evidence to support the spinal processing of pain signals has come to light. Cognitive and affective aspects of the pain experience indicate the importance of supraspinal structures, but the biological mechanisms have remained inadequately explored. Within the past decade, imaging techniques have emerged that enable in vivo assessment of the central opioidergic system and the central processing of pain. The two most important imaging modalities to this end are functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). This article will describe the underlying principles of these techniques and explain their importance in determining the loci of opioidergic pathways and their neuromodulatory influence on acute and chronic pain conditions, role in placebo effects, implication in drug dependence, and potential role in studying the analgesic efficacy of new drugs.

scholarly journals Beyond the H&E: Advanced Technologies for in situ Tissue Biomarker Imaging

ILAR Journal ◽  
2018 ◽  
Vol 59 (1) ◽  
pp. 51-65 ◽  
Author(s):  
Lauren E Himmel ◽  
Troy A Hackett ◽  
Jessica L Moore ◽  
Wilson R Adams ◽  
Giju Thomas ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Imaging Techniques ◽  
Imaging Mass Spectrometry ◽  
Medical Engineering ◽  
Optical Methods ◽  
Tissue Samples ◽  
Tissue Sections ◽  
Tissue Biomarker

AbstractFor decades, histopathology with routine hematoxylin and eosin staining has been and remains the gold standard for reaching a morphologic diagnosis in tissue samples from humans and veterinary species. However, within the past decade, there has been exponential growth in advanced techniques for in situ tissue biomarker imaging that bridge the divide between anatomic and molecular pathology. It is now possible to simultaneously observe localization and expression magnitude of multiple protein, nucleic acid, and molecular targets in tissue sections and apply machine learning to synthesize vast, image-derived datasets. As these technologies become more sophisticated and widely available, a team-science approach involving subspecialists with medical, engineering, and physics backgrounds is critical to upholding quality and validity in studies generating these data. The purpose of this manuscript is to detail the scientific premise, tools and training, quality control, and data collection and analysis considerations needed for the most prominent advanced imaging technologies currently applied in tissue sections: immunofluorescence, in situ hybridization, laser capture microdissection, matrix-assisted laser desorption ionization imaging mass spectrometry, and spectroscopic/optical methods. We conclude with a brief overview of future directions for ex vivo and in vivo imaging techniques.

New Perspectives on Alzheimer's Disease: Studies with Positron Emission Tomography

1991 ◽  
Vol 3 (S1) ◽  
pp. 61-67
Author(s):  
P. J. Tyrrell ◽  
R. S. J. Frackowiak
Keyword(s):  
Positron Emission Tomography ◽  
Dopaminergic System ◽  
Cerebral Metabolism ◽  
Imaging Techniques ◽  
Cognitive Disorders ◽  
Emission Tomography ◽  
Alzheimer Type ◽  
Positron Emission ◽  
Abnormal Metabolism

Positron Emission Tomography (PET) is a quantitative technique which can be used to measure regional values of cerebral metabolism, or uptake of radio-labeled tracers, in the living human. While structural scans (CT or MRI) may be normal in the degenerative dementias, or show generalized atrophy, functional imaging techniques allow differentiation of subtypes of dementias according to patterns of abnormal metabolism. This paper describes some of the variety of alterations in patterns of energy metabolism that may be observed in degenerative cognitive disorders and their correlations with clinical subtypes, together with an in vivo study of the dopaminergic system in subtypes of patients with dementia of the Alzheimer type (DAT).

New advance in breast cancer pathology and imaging

2019 ◽  
Vol 15 (23) ◽  
pp. 2707-2722 ◽  
Author(s):  
Nicoletta Urbano ◽  
Manuel Scimeca ◽  
Rita Bonfiglio ◽  
Elena Bonanno ◽  
Orazio Schillaci
Keyword(s):  
Breast Cancer ◽  
Imaging Techniques ◽  
Emission Tomography ◽  
Intrinsic Variability ◽  
Imaging Diagnostics ◽  
Medical Specialties ◽  
Cancer Pathology ◽  
Positron Emission ◽  
Breast Cancer Pathology

The improvement of knowledge concerning the pathology of breast cancer could provide the rationale for the development of new imaging diagnostic protocols. Indeed, as for the microcalcifications, new histopathological markers can be used as target for in vivo early detection of breast cancer lesions by using molecular imaging techniques such as positron emission tomography. Specifically, the mutual contribution of these medical specialties can ‘nourish’ the dream of a personalized medicine that takes into account the intrinsic variability of breast cancer. In this review, we report the main discoveries concerning breast cancer pathology highlighting the possible cooperation between the departments of anatomic pathology and imaging diagnostics.

scholarly journals Novel application of complementary imaging techniques to examine in vivo glucose metabolism in the kidney

2016 ◽  
Vol 310 (8) ◽  
pp. F717-F725 ◽  
Author(s):  
Takashi Hato ◽  
Allon N. Friedman ◽  
Henry Mang ◽  
Zoya Plotkin ◽  
Shataakshi Dube ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Imaging Techniques ◽  
Multiphoton Microscopy ◽  
Tracer Uptake ◽  
Mitochondrial Potential ◽  
Pharmacological Inhibition ◽  
Positron Emission ◽  
Tracer Kinetic ◽  
Preclinical And Clinical Studies

The metabolic status of the kidney is a determinant of injury susceptibility and a measure of progression for many disease processes; however, noninvasive modalities to assess kidney metabolism are lacking. In this study, we employed positron emission tomography (PET) and intravital multiphoton microscopy (MPM) to assess cortical and proximal tubule glucose tracer uptake, respectively, following experimental perturbations of kidney metabolism. Applying dynamic image acquisition PET with 2-18fluoro-2-deoxyglucose (18F-FDG) and tracer kinetic modeling, we found that an intracellular compartment in the cortex of the kidney could be distinguished from the blood and urine compartments in animals. Given emerging literature that the tumor suppressor protein p53 is an important regulator of cellular metabolism, we demonstrated that PET imaging was able to discern a threefold increase in cortical 18F-FDG uptake following the pharmacological inhibition of p53 in animals. Intravital MPM with the fluorescent glucose analog 2-[ N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) provided increased resolution and corroborated these findings at the level of the proximal tubule. Extending our observation of p53 inhibition on proximal tubule glucose tracer uptake, we demonstrated by intravital MPM that pharmacological inhibition of p53 diminishes mitochondrial potential difference. We provide additional evidence that inhibition of p53 alters key metabolic enzymes regulating glycolysis and increases intermediates of glycolysis. In summary, we provide evidence that PET is a valuable tool for examining kidney metabolism in preclinical and clinical studies, intravital MPM is a powerful adjunct to PET in preclinical studies of metabolism, and p53 inhibition alters basal kidney metabolism.

scholarly journals Diagnosis of Pancreatic Ductal Adenocarcinoma by Immuno-Positron Emission Tomography

2021 ◽  
Vol 10 (6) ◽  
pp. 1151
Author(s):  
Ruth González-Gómez ◽  
Roberto A. Pazo-Cid ◽  
Luis Sarría ◽  
Miguel Ángel Morcillo ◽  
Alberto J. Schuhmacher
Keyword(s):  
Positron Emission Tomography ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Imaging Techniques ◽  
Metastatic Tumor ◽  
Emission Tomography ◽  
Whole Body ◽  
Ductal Adenocarcinoma ◽  
Non Invasive ◽  
Positron Emission

Diagnosis of pancreatic ductal adenocarcinoma (PDAC) by current imaging techniques is useful and widely used in the clinic but presents several limitations and challenges, especially in small lesions that frequently cause radiological tumors infra-staging, false-positive diagnosis of metastatic tumor recurrence, and common occult micro-metastatic disease. The revolution in cancer multi-“omics” and bioinformatics has uncovered clinically relevant alterations in PDAC that still need to be integrated into patients’ clinical management, urging the development of non-invasive imaging techniques against principal biomarkers to assess and incorporate this information into the clinical practice. “Immuno-PET” merges the high target selectivity and specificity of antibodies and engineered fragments toward a given tumor cell surface marker with the high spatial resolution, sensitivity, and quantitative capabilities of positron emission tomography (PET) imaging techniques. In this review, we detail and provide examples of the clinical limitations of current imaging techniques for diagnosing PDAC. Furthermore, we define the different components of immuno-PET and summarize the existing applications of this technique in PDAC. The development of novel immuno-PET methods will make it possible to conduct the non-invasive diagnosis and monitoring of patients over time using in vivo, integrated, quantifiable, 3D, whole body immunohistochemistry working like a “virtual biopsy”.

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