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Molecular Imaging in Diabetes, Obesity, and Infections 2.0

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Guest Editor
Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8542, USA
Interests: molecular imaging of fat metabolism; bone metabolism; molecular imaging of infections; clinical trials in molecular imaging and nuclear medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous successful Special Issue, “Molecular Imaging in Diabetes, Obesity, and Infections”.

Molecular imaging is an exciting field that can be defined as the visualization and/or measurement of biological or biochemical processes at cellular and molecular levels. It is performed in preclinical models and in living human subjects. By necessity, molecular imaging is multidisciplinary, applying synthetic and radiochemistry, molecular biology, (patho)physiology, and multiple imaging techniques. It leverages both endogenous and exogenous imaging probes to generate detectable signals. Molecular imaging techniques include optical and optoacoustic methods, ultrasound, molecular computed tomography, magnetic resonance imaging, and spectroscopy. Molecular imaging is used to diagnose diseases, assess treatment responses, and define the underlying pathophysiology of a disease process. To this end, molecular imaging has been used to non-invasively visualize aberrant tumor metabolism, bacterial infections, beta-cell mass and function, and adipocyte metabolism. This Special Issue focuses on developing and implementing molecular imaging strategies for research in obesity, diabetes, infectious diseases, and tumor metabolism. We welcome original research and review articles.

Prof. Orhan K. Öz
Guest Editor

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Keywords

  • radionuclide probes
  • SPECT imaging
  • PET imaging
  • MRI
  • optical imaging
  • beta cells
  • diabetes
  • obesity
  • bacterial infections

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Related Special Issue

Published Papers (5 papers)

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Research

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14 pages, 3426 KiB  
Article
Comparison of BMIPP-SPECT/CT to 18FDG-PET/CT for Imaging Brown or Browning Fat in a Preclinical Model
by Joseph A. Frankl, Yu An, Amber Sherwood, Guiyang Hao, Feng-Yun Huang, Pawan Thapa, Deborah J. Clegg, Xiankai Sun, Philipp E. Scherer and Orhan K. Öz
Int. J. Mol. Sci. 2022, 23(9), 4880; https://doi.org/10.3390/ijms23094880 - 28 Apr 2022
Cited by 1 | Viewed by 2798
Abstract
Obesity is a leading cause of preventable death and morbidity. To elucidate the mechanisms connecting metabolically active brown adipose tissue (BAT) and metabolic health may provide insights into methods of treatment for obesity-related conditions. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) [...] Read more.
Obesity is a leading cause of preventable death and morbidity. To elucidate the mechanisms connecting metabolically active brown adipose tissue (BAT) and metabolic health may provide insights into methods of treatment for obesity-related conditions. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) is traditionally used to image human BAT activity. However, the primary energy source of BAT is derived from intracellular fatty acids and not glucose. Beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) is a fatty acid analogue amenable to in vivo imaging by single photon emission computed tomography/CT (SPECT/CT) when radiolabeled with iodine isotopes. In this study, we compare the use of 18FDG-PET/CT and 125I-BMIPP-SPECT/CT for fat imaging to ascertain whether BMIPP is a more robust candidate for the non-invasive evaluation of metabolically active adipose depots. Interscapular BAT, inguinal white adipose tissue (iWAT), and gonadal white adipose tissue (gWAT) uptake of 18FDG and 125I-BMIPP was quantified in mice following treatment with the BAT-stimulating drug CL-316,243 or saline vehicle control. After CL-316,243 treatment, uptake of both radiotracers increased in BAT and iWAT. The standard uptake value (SUVmean) for 18FDG and 125I-BMIPP significantly correlated in these depots, although uptake of 125I-BMIPP in BAT and iWAT more closely mimicked the fold-change in metabolic rate as measured by an extracellular flux analyzer. Herein, we find that imaging BAT with the radioiodinated fatty acid analogue BMIPP yields more physiologically relevant data than 18FDG-PET/CT, and its conventional use may be a pivotal tool for evaluating BAT in both mice and humans. Full article
(This article belongs to the Special Issue Molecular Imaging in Diabetes, Obesity, and Infections 2.0)
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16 pages, 3413 KiB  
Article
Fluorescence Microscopy-Based Quantitation of GLUT4 Translocation: High Throughput or High Content?
by Verena Stadlbauer, Peter Lanzerstorfer, Cathrina Neuhauser, Florian Weber, Flora Stübl, Petra Weber, Michael Wagner, Birgit Plochberger, Stefan Wieser, Herbert Schneckenburger and Julian Weghuber
Int. J. Mol. Sci. 2020, 21(21), 7964; https://doi.org/10.3390/ijms21217964 - 27 Oct 2020
Cited by 10 | Viewed by 3457
Abstract
Due to the global rise of type 2 diabetes mellitus (T2DM) in combination with insulin resistance, novel compounds to efficiently treat this pandemic disease are needed. Screening for compounds that induce the translocation of glucose transporter 4 (GLUT4) from the intracellular compartments to [...] Read more.
Due to the global rise of type 2 diabetes mellitus (T2DM) in combination with insulin resistance, novel compounds to efficiently treat this pandemic disease are needed. Screening for compounds that induce the translocation of glucose transporter 4 (GLUT4) from the intracellular compartments to the plasma membrane in insulin-sensitive tissues is an innovative strategy. Here, we compared the applicability of three fluorescence microscopy-based assays optimized for the quantitation of GLUT4 translocation in simple cell systems. An objective-type scanning total internal reflection fluorescence (TIRF) microscopy approach was shown to have high sensitivity but only moderate throughput. Therefore, we implemented a prism-type TIR reader for the simultaneous analysis of large cell populations grown in adapted microtiter plates. This approach was found to be high throughput and have sufficient sensitivity for the characterization of insulin mimetic compounds in live cells. Finally, we applied confocal microscopy to giant plasma membrane vesicles (GPMVs) formed from GLUT4-expressing cells. While this assay has only limited throughput, it offers the advantage of being less sensitive to insulin mimetic compounds with high autofluorescence. In summary, the combined implementation of different fluorescence microscopy-based approaches enables the quantitation of GLUT4 translocation with high throughput and high content. Full article
(This article belongs to the Special Issue Molecular Imaging in Diabetes, Obesity, and Infections 2.0)
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Review

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32 pages, 2741 KiB  
Review
Pathophysiology and Molecular Imaging of Diabetic Foot Infections
by Katie Rubitschung, Amber Sherwood, Andrew P. Crisologo, Kavita Bhavan, Robert W. Haley, Dane K. Wukich, Laila Castellino, Helena Hwang, Javier La Fontaine, Avneesh Chhabra, Lawrence Lavery and Orhan K. Öz
Int. J. Mol. Sci. 2021, 22(21), 11552; https://doi.org/10.3390/ijms222111552 - 26 Oct 2021
Cited by 29 | Viewed by 11823
Abstract
Diabetic foot infection is the leading cause of non-traumatic lower limb amputations worldwide. In addition, diabetes mellitus and sequela of the disease are increasing in prevalence. In 2017, 9.4% of Americans were diagnosed with diabetes mellitus (DM). The growing pervasiveness and financial implications [...] Read more.
Diabetic foot infection is the leading cause of non-traumatic lower limb amputations worldwide. In addition, diabetes mellitus and sequela of the disease are increasing in prevalence. In 2017, 9.4% of Americans were diagnosed with diabetes mellitus (DM). The growing pervasiveness and financial implications of diabetic foot infection (DFI) indicate an acute need for improved clinical assessment and treatment. Complex pathophysiology and suboptimal specificity of current non-invasive imaging modalities have made diagnosis and treatment response challenging. Current anatomical and molecular clinical imaging strategies have mainly targeted the host’s immune responses rather than the unique metabolism of the invading microorganism. Advances in imaging have the potential to reduce the impact of these problems and improve the assessment of DFI, particularly in distinguishing infection of soft tissue alone from osteomyelitis (OM). This review presents a summary of the known pathophysiology of DFI, the molecular basis of current and emerging diagnostic imaging techniques, and the mechanistic links of these imaging techniques to the pathophysiology of diabetic foot infections. Full article
(This article belongs to the Special Issue Molecular Imaging in Diabetes, Obesity, and Infections 2.0)
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18 pages, 12045 KiB  
Review
Molecular Imaging of Brown Adipose Tissue Mass
by Jing Yang, Haili Zhang, Kadirya Parhat, Hui Xu, Mingshuang Li, Xiangyu Wang and Chongzhao Ran
Int. J. Mol. Sci. 2021, 22(17), 9436; https://doi.org/10.3390/ijms22179436 - 30 Aug 2021
Cited by 21 | Viewed by 5577
Abstract
Brown adipose tissue (BAT), a uniquely thermogenic tissue that plays an important role in metabolism and energy expenditure, has recently become a revived target in the fight against metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD). Different from white [...] Read more.
Brown adipose tissue (BAT), a uniquely thermogenic tissue that plays an important role in metabolism and energy expenditure, has recently become a revived target in the fight against metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD). Different from white adipose tissue (WAT), the brown adipocytes have distinctive features including multilocular lipid droplets, a large number of mitochondria, and a high expression of uncoupling protein-1 (UCP-1), as well as abundant capillarity. These histologic characteristics provide an opportunity to differentiate BAT from WAT using imaging modalities, such as PET/CT, SPECT/CT, MRI, NIRF and Ultrasound. However, most of the reported imaging methods were BAT activation dependent, and the imaging signals could be affected by many factors, including environmental temperatures and the states of the sympathetic nervous system. Accurate BAT mass detection methods that are independent of temperature and hormone levels have the capacity to track the development and changes of BAT throughout the lifetime of mammals, and such methods could be very useful for the investigation of potential BAT-related therapies. In this review, we focus on molecular imaging modalities that can detect and quantify BAT mass. In addition, their detection mechanism and limitations will be discussed as well. Full article
(This article belongs to the Special Issue Molecular Imaging in Diabetes, Obesity, and Infections 2.0)
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15 pages, 23641 KiB  
Review
Diabetes, Obesity, and Inflammation: Impact on Clinical and Radiographic Features of Breast Cancer
by Braden Miller, Hunter Chalfant, Alexandra Thomas, Elizabeth Wellberg, Christina Henson, Molly W. McNally, William E. Grizzle, Ajay Jain and Lacey R. McNally
Int. J. Mol. Sci. 2021, 22(5), 2757; https://doi.org/10.3390/ijms22052757 - 9 Mar 2021
Cited by 18 | Viewed by 4916
Abstract
Obesity, diabetes, and inflammation increase the risk of breast cancer, the most common malignancy in women. One of the mainstays of breast cancer treatment and improving outcomes is early detection through imaging-based screening. There may be a role for individualized imaging strategies for [...] Read more.
Obesity, diabetes, and inflammation increase the risk of breast cancer, the most common malignancy in women. One of the mainstays of breast cancer treatment and improving outcomes is early detection through imaging-based screening. There may be a role for individualized imaging strategies for patients with certain co-morbidities. Herein, we review the literature regarding the accuracy of conventional imaging modalities in obese and diabetic women, the potential role of anti-inflammatory agents to improve detection, and the novel molecular imaging techniques that may have a role for breast cancer screening in these patients. We demonstrate that with conventional imaging modalities, increased sensitivity often comes with a loss of specificity, resulting in unnecessary biopsies and overtreatment. Obese women have body size limitations that impair image quality, and diabetes increases the risk for dense breast tis-sue. Increased density is known to obscure the diagnosis of cancer on routine screening mammography. Novel molecu-lar imaging agents with targets such as estrogen receptor, human epidermal growth factor receptor 2 (HER2), pyrimi-dine analogues, and ligand-targeted receptor probes, among others, have potential to reduce false positive results. They can also improve detection rates with increased resolution and inform therapeutic decision making. These emerg-ing imaging techniques promise to improve breast cancer diagnosis in obese patients with diabetes who have dense breasts, but more work is needed to validate their clinical application. Full article
(This article belongs to the Special Issue Molecular Imaging in Diabetes, Obesity, and Infections 2.0)
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