Molecular Imaging: a Novel Tool To Visualize Pathogenesis of Infections In Situ

Molecular imaging is an emerging technology that enables the noninvasive visualization, characterization, and quantification of molecular events within living subjects. Positron emission tomography (PET) is a clinically available molecular imaging tool with significant potential to study pathogenesis of infections in humans. ABSTRACT Molecular imaging is an emerging technology that enables the noninvasive visualization, characterization, and quantification of molecular events within living subjects. Positron emission tomography (PET) is a clinically available molecular imaging tool with significant potential to study pathogenesis of infections in humans. PET enables dynamic assessment of infectious processes within the same subject with high temporal and spatial resolution and obviates the need for invasive tissue sampling, which is difficult in patients and generally limited to a single time point, even in animal models. This review presents current state-of-the-art concepts on the application of molecular imaging for infectious diseases and details how PET imaging can facilitate novel insights into infectious processes, ongoing development of pathogen-specific imaging, and simultaneous in situ measurements of intralesional antimicrobial pharmacokinetics in multiple compartments, including privileged sites. Finally, the potential clinical applications of this promising technology are also discussed.

[1]  M. Bogyo,et al.  A Clinical Wide-Field Fluorescence Endoscopic Device for Molecular Imaging Demonstrating Cathepsin Protease Activity in Colon Cancer , 2016, Molecular Imaging and Biology.

[2]  V. Havlíček,et al.  Early and Non-invasive Diagnosis of Aspergillosis Revealed by Infection Kinetics Monitored in a Rat Model , 2018, Front. Microbiol..

[3]  T. van Gelder,et al.  Clinical applications of population pharmacokinetic models of antibiotics: Challenges and perspectives , 2018, Pharmacological research.

[4]  J. Hoxie,et al.  Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy–treated macaques , 2015, Nature Methods.

[5]  Bruno Jedynak,et al.  Noninvasive Pulmonary [18F]-2-Fluoro-Deoxy-d-Glucose Positron Emission Tomography Correlates with Bactericidal Activity of Tuberculosis Drug Treatment , 2009, Antimicrobial Agents and Chemotherapy.

[6]  J. Bomanji,et al.  Comparison of 99mTc Infecton imaging with radiolabelled white-cell imaging in the evaluation of bacterial infection , 1996, The Lancet.

[7]  Ramy A. Fodah,et al.  Validation of 2-18F-Fluorodeoxysorbitol as a Potential Radiopharmaceutical for Imaging Bacterial Infection in the Lung , 2018, The Journal of Nuclear Medicine.

[8]  G. Lucignani The many roads to infection imaging , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[9]  W. J. Perry,et al.  Integrated molecular imaging reveals tissue heterogeneity driving host-pathogen interactions , 2018, Science Translational Medicine.

[10]  D. Hammoud,et al.  Molecular imaging of bacterial infections: Overcoming the barriers to clinical translation , 2019, Science Translational Medicine.

[11]  M. Javadi,et al.  Recent paradigm shifts in molecular cardiac imaging-Establishing precision cardiology through novel 18F-labeled PET radiotracers. , 2019, Trends in cardiovascular medicine.

[12]  P. Tonge,et al.  Noninvasive Determination of 2-[18F]-Fluoroisonicotinic Acid Hydrazide Pharmacokinetics by Positron Emission Tomography in Mycobacterium tuberculosis-Infected Mice , 2012, Antimicrobial Agents and Chemotherapy.

[13]  Dongin Kim,et al.  Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity. , 2011, Nature materials.

[14]  Christopher H Contag,et al.  Specific Imaging of Bacterial Infection Using 6″-18F-Fluoromaltotriose: A Second-Generation PET Tracer Targeting the Maltodextrin Transporter in Bacteria , 2017, The Journal of Nuclear Medicine.

[15]  M. Pomper,et al.  Biodistribution and Radiation Dosimetry of 124I-DPA-713, a PET Radiotracer for Macrophage-Associated Inflammation , 2018, The Journal of Nuclear Medicine.

[16]  V. Ivaturi,et al.  Noninvasive 11C-rifampin positron emission tomography reveals drug biodistribution in tuberculous meningitis , 2018, Science Translational Medicine.

[17]  M. Pomper,et al.  Radioiodinated DPA-713 Imaging Correlates with Bactericidal Activity of Tuberculosis Treatments in Mice , 2014, Antimicrobial Agents and Chemotherapy.

[18]  P. Tonge,et al.  Pharmacokinetic and Pharmacodynamics Relationships , 2017 .

[19]  R. Weissleder Molecular Imaging in Cancer , 2006, Science.

[20]  Cathrine A. McKenzie Antibiotic dosing in critical illness. , 2011, The Journal of antimicrobial chemotherapy.

[21]  L. Dodd,et al.  Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure , 2016, Nature Medicine.

[22]  H. Yamaguchi,et al.  Cerebral metabolic reduction in severe malaria: fluorodeoxyglucose-positron emission tomography imaging in a primate model of severe human malaria with cerebral involvement. , 2004, The American journal of tropical medicine and hygiene.

[23]  D. Mollura,et al.  Mouse model of pulmonary cavitary tuberculosis and expression of matrix metalloproteinase-9 , 2016, Disease Models & Mechanisms.

[24]  Matthew D. Zimmerman,et al.  The association between sterilizing activity and drug distribution into tuberculosis lesions , 2015, Nature Medicine.

[25]  M. Pomper,et al.  Noninvasive molecular imaging of tuberculosis-associated inflammation with radioiodinated DPA-713. , 2013, The Journal of infectious diseases.

[26]  L. Dodd,et al.  Increased Metabolic Activity on 18F-Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography in Human Immunodeficiency Virus–Associated Immune Reconstitution Inflammatory Syndrome , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[27]  D. Le Guludec,et al.  Inability of 99mTc-ciprofloxacin scintigraphy to discriminate between septic and sterile osteoarticular diseases. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  Jace W. Jones,et al.  Sustained virologic control in SIV+ macaques after antiretroviral and alpha(4)beta(7) antibody therapy , 2017 .

[29]  A. Lupetti,et al.  Detection of fungal infections using radiolabeled antifungal agents. , 2005, Current drug targets.

[30]  V. Saini,et al.  A Systematic Approach for Developing Bacteria-Specific Imaging Tracers , 2017, The Journal of Nuclear Medicine.

[31]  M. Behr,et al.  Revisiting the timetable of tuberculosis , 2018, British Medical Journal.

[32]  D. Mollura,et al.  Molecular Imaging of Influenza and Other Emerging Respiratory Viral Infections , 2011, The Journal of infectious diseases.

[33]  I. C. Kok,et al.  Molecular Imaging in Cancer Drug Development , 2018, The Journal of Nuclear Medicine.

[34]  Jace W. Jones,et al.  Sustained virologic control in SIV+ macaques after antiretroviral and α4β7 antibody therapy , 2016, Science.

[35]  W. Moses,et al.  Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care , 2018, The Journal of Nuclear Medicine.

[36]  Zibo Li,et al.  Infection Imaging With (18)F-FDS and First-in-Human Evaluation. , 2016, Nuclear medicine and biology.

[37]  K. Dooley,et al.  Determination of [11C]Rifampin Pharmacokinetics within Mycobacterium tuberculosis-Infected Mice by Using Dynamic Positron Emission Tomography Bioimaging , 2015, Antimicrobial Agents and Chemotherapy.

[38]  V. Havlíček,et al.  Imaging of Pseudomonas aeruginosa infection with Ga-68 labelled pyoverdine for positron emission tomography , 2018, Scientific Reports.

[39]  M. Pomper,et al.  Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography , 2014, Science Translational Medicine.

[40]  G. Schoolnik,et al.  Corrigendum: Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure , 2017, Nature Medicine.

[41]  M. Daly,et al.  Ipr1 gene mediates innate immunity to tuberculosis , 2005, Nature.

[42]  M. Ohliger,et al.  [11C]Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism. , 2018, ACS infectious diseases.

[43]  K. Pienta,et al.  Prostate-Specific Membrane Antigen (PSMA)-Targeted PET Imaging of Prostate Cancer: An Update on Important Pitfalls. , 2019, Seminars in nuclear medicine.

[44]  Young T. Hong,et al.  Hypoxia and tissue destruction in pulmonary TB , 2016, Thorax.

[45]  S. Solomon,et al.  Antibiotic resistance threats in the United States: stepping back from the brink. , 2014, American family physician.

[46]  Robert M. DiFazio,et al.  PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis , 2016, PLoS pathogens.

[47]  W. Bishai,et al.  Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions. , 2012, The Journal of infectious diseases.

[48]  S. Gambhir,et al.  Investigation of 6-[18F]-Fluoromaltose as a Novel PET Tracer for Imaging Bacterial Infection , 2014, PloS one.

[49]  M. Ohliger,et al.  Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers , 2017, Scientific Reports.

[50]  Q. Nguyen,et al.  Molecular imaging for cancer diagnosis and surgery. , 2014, Advanced drug delivery reviews.

[51]  E. Weinstein,et al.  Biodistribution and pharmacokinetics of antimicrobials , 2017 .

[52]  G. Borm,et al.  Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. , 2013, The Lancet. Infectious diseases.

[53]  A. Lackner,et al.  The non‐human primate model of tuberculosis , 2012, Journal of medical primatology.

[54]  P. Tonge,et al.  Positron Emission Tomography Imaging with 2-[18F]F-p-Aminobenzoic Acid Detects Staphylococcus aureus Infections and Monitors Drug Response , 2018, ACS infectious diseases.

[55]  Ralph Weissleder,et al.  Molecular imaging of cardiovascular disease. , 2007, Circulation.

[56]  P. Price,et al.  PET for in vivo pharmacokinetic and pharmacodynamic measurements. , 2002, European journal of cancer.

[57]  S. Lapage,et al.  Biochemical Tests for Identification of Medical Bacteria , 1976 .

[58]  Sanjay K. Jain The Promise of Molecular Imaging in the Study and Treatment of Infectious Diseases , 2017, Molecular Imaging and Biology.

[59]  G. Gensini,et al.  Studies on the gaseous content of tuberculous cavities. , 1959, The American review of respiratory disease.

[60]  D. Mankoff,et al.  Bacterial infection imaging with [18F]fluoropropyl-trimethoprim , 2017, Proceedings of the National Academy of Sciences.

[61]  C. Barry,et al.  Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses , 2015, Immunological reviews.

[62]  A. van Waarde,et al.  [18F]FHPG Positron Emission Tomography for Detection of Herpes Simplex Virus (HSV) in Experimental HSV Encephalitis , 2005, Journal of Virology.

[63]  C. Thornton Development of an Immunochromatographic Lateral-Flow Device for Rapid Serodiagnosis of Invasive Aspergillosis , 2008, Clinical and Vaccine Immunology.

[64]  D. Hammoud Molecular Imaging of Inflammation: Current Status , 2016, The Journal of Nuclear Medicine.

[65]  Sanjiv S Gambhir,et al.  A molecular imaging primer: modalities, imaging agents, and applications. , 2012, Physiological reviews.

[66]  M. Lisanti,et al.  Imaging of small-animal models of infectious diseases. , 2013, The American journal of pathology.

[67]  F. Jaffer,et al.  Metabolic and Molecular Imaging of Atherosclerosis and Venous Thromboembolism , 2017, The Journal of Nuclear Medicine.

[68]  Aaron S. Andalman,et al.  Structural and molecular interrogation of intact biological systems , 2013, Nature.

[69]  M. Levison,et al.  Pharmacokinetics and pharmacodynamics of antibacterial agents. , 2009, Infectious disease clinics of North America.

[70]  Kyle M. Jones,et al.  Differentiating lung cancer and infection based on measurements of extracellular pH with acidoCEST MRI , 2019, Scientific Reports.

[71]  L. Younes,et al.  Imaging the Evolution of Reactivation Pulmonary Tuberculosis in Mice Using 18F-FDG PET , 2014, The Journal of Nuclear Medicine.

[72]  Nicholas A. Be,et al.  Bacterial Thymidine Kinase as a Non-Invasive Imaging Reporter for Mycobacterium tuberculosis in Live Animals , 2009, PloS one.

[73]  S. Vallabhajosula,et al.  Clinically proven radiopharmaceuticals for infection imaging: mechanisms and applications. , 2009, Seminars in nuclear medicine.

[74]  T. Vijayan,et al.  Using Nuclear Medicine Imaging Wisely in Diagnosing Infectious Diseases , 2017, Open forum infectious diseases.

[75]  Mac Faddin,et al.  Biochemical tests for identification of medical bacteria , 1976 .

[76]  Ophir Vermesh,et al.  Toward achieving precision health , 2018, Science Translational Medicine.

[77]  Peter Herscovitch,et al.  PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis , 2014, Science Translational Medicine.

[78]  Winfried Boos,et al.  Maltose/Maltodextrin System of Escherichia coli: Transport, Metabolism, and Regulation , 1998, Microbiology and Molecular Biology Reviews.

[79]  C. Thornton Molecular Imaging of Invasive Pulmonary Aspergillosis Using ImmunoPET/MRI: The Future Looks Bright , 2018, Front. Microbiol..

[80]  J. Andrews,et al.  Determination of minimum inhibitory concentrations. , 2001, The Journal of antimicrobial chemotherapy.

[81]  Z. Bhujwalla,et al.  Microglia activation in a pediatric rabbit model of tuberculous meningitis , 2016, Disease Models & Mechanisms.

[82]  Joel S. Freundlich,et al.  Radiosynthesis and PET Bioimaging of 76Br-Bedaquiline in a Murine Model of Tuberculosis. , 2019, ACS infectious diseases.

[83]  M. Chase,et al.  Digitally Barcoding Mycobacterium tuberculosis Reveals In Vivo Infection Dynamics in the Macaque Model of Tuberculosis , 2017, mBio.

[84]  D. Tobin,et al.  Adventures within the speckled band: heterogeneity, angiogenesis, and balanced inflammation in the tuberculous granuloma , 2015, Immunological reviews.

[85]  E. Fischer,et al.  ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo , 2016, Proceedings of the National Academy of Sciences.