Skip to main content
SpringerLink
Log in
Book cover

Pharmaco-Imaging in Drug and Biologics Development pp 271–290Cite as

Preclinical Imaging in BSL-3 and BSL-4 Environments: Imaging Pathophysiology of Highly Pathogenic Infectious Diseases

  • Chapter
  • First Online:

  • 1216 Accesses

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 8))

Abstract

Structural and functional imaging are emerging as powerful tools for studying highly pathogenic infectious disease processes. Nuclear imaging modalities and sophisticated radiolabeled probes can be used to track physiological or biochemical processes associated with viral infection. Magnetic resonance imaging can provide anatomical images with exquisite soft tissue contrast, while magnetic resonance spectroscopy can measure the relative amounts of certain metabolites in a given tissue. However, conducting medical imaging studies in a high-containment laboratory requires advanced applications and modification not only of image acquisition and analysis processes but also of the imaging equipment. Processes such as ex vivo labeling of cells are hampered by the personal protective equipment required for the safety of laboratory personnel. Modification of medical imaging equipment can prevent contamination of the equipment. Regardless of the challenges involved, medical imaging could provide valuable information to researchers developing therapeutics against highly pathogenic infectious diseases.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Bading JR, Shields AF (2008) Imaging of cell proliferation: status and prospects. J Nucl Med 49(Suppl 2):64S–80S

    Article  PubMed  CAS  Google Scholar 

  • Beckmann N et al (2003) Macrophage infiltration into the rat knee detected by MRI in a model of antigen-induced arthritis. Magn Reson Med 49(6):1047–1055

    Article  PubMed  Google Scholar 

  • Bellani G et al (2010) Imaging of lung inflammation during severe influenza A: H1N1. Intensive Care Med 36(4):717–718

    Article  PubMed  Google Scholar 

  • Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69(3):89–95

    Article  Google Scholar 

  • Blaimer M et al (2004) SMASH, SENSE, PILS, GRAPPA: how to choose the optimal method. Top Magn Reson Imaging 15(4):223–236

    Article  PubMed  Google Scholar 

  • Bray M et al (2010) Radiolabeled antiviral drugs and antibodies as virus-specific imaging probes. Antiviral Res 88(2):129–142

    Article  PubMed  CAS  Google Scholar 

  • Brunetti A et al (1989) Reversal of brain metabolic abnormalities following treatment of AIDS dementia complex with 3′-azido-2′,3′-dideoxythymidine (AZT, zidovudine): a PET-FDG study. J Nucl Med 30(5):581–590

    PubMed  CAS  Google Scholar 

  • Brust D et al (2006) Fluorodeoxyglucose imaging in healthy subjects with HIV infection: impact of disease stage and therapy on pattern of nodal activation. AIDS 20(7):985–993

    Article  PubMed  Google Scholar 

  • Bulte JW (2009) In vivo MRI cell tracking: clinical studies. Am J Roentgenol 193(2):314–325

    Article  Google Scholar 

  • Burton JM et al (2004) Neurological manifestations of West Nile virus infection. Can J Neurol Sci 31(2):185–193

    PubMed  Google Scholar 

  • Buscombe JR, Oyen WJ, Corstens FH (1995) Use of polyclonal IgG in HIV infection and AIDS. Q J Nucl Med 39(3):212–220

    PubMed  CAS  Google Scholar 

  • Chaljub G et al (2001) Projectile cylinder accidents resulting from the presence of ferromagnetic nitrous oxide or oxygen tanks in the MR suite. Am J Roentgenol 177(1):27–30

    Article  CAS  Google Scholar 

  • Cherry SR, Sorenson JA, Phelps ME (2003) The gamma camera: performance characteristics. In: Physics in nuclear medicine. Saunders, Philadephia, PA

    Google Scholar 

  • Cyran CC et al (2012) Permeability to macromolecular contrast media quantified by dynamic MRI correlates with tumor tissue assays of vascular endothelial growth factor (VEGF). Eur J Radiol 81(5):891–896

    Article  PubMed  Google Scholar 

  • Dannels WR et al (2008) Integrated system of MRI RF loop coils plus spacing fixtures with biocontainment tubes. WIPO Patent Application. PCT/US2008 073512, filed June 19, 2008

    Google Scholar 

  • de Kok-Mercado F, Kutlak F, Jahrling PB (2011) The NIAID integrated research facility at Fort Detrick. Appl Biosafety 16(2):58–66

    Google Scholar 

  • Di Mascio M et al (2009) Antiretroviral tissue kinetics: in vivo imaging using positron emission tomography. Antimicrob Agents Chemother 53(10):4086–4095

    Article  PubMed  Google Scholar 

  • Dotti G et al (2009) Repetitive noninvasive monitoring of HSV1-tk-expressing T cells intravenously infused into nonhuman primates using positron emission tomography and computed tomography with 18F-FEAU. Mol Imaging 8(4):230–237

    PubMed  Google Scholar 

  • Dyall J et al (2011) Evaluation of monkeypox disease progression by molecular imaging. J Infect Dis 204(12):1902–1911

    Article  PubMed  CAS  Google Scholar 

  • Dyall J et al (2012) Assessment of longitudinal changes in 18FDG uptake in bone marrow and lymph node and in lymph node volume in nonhuman primate model of monkeypox infection. World Molecular Imaging Congress Dublin, Ireland, Sep 5–8 2012

    Google Scholar 

  • Ferro-Flores G, Ocampo-Garcia BE, Melendez-Alafort L (2012) Development of specific radiopharmaceuticals for infection imaging by targeting infectious micro-organisms. Curr Pharm Des 18(8):1098–1106

    Article  PubMed  CAS  Google Scholar 

  • Floris S et al (2004) Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis: a quantitative MRI study. Brain 127(Pt 3):616–627

    PubMed  CAS  Google Scholar 

  • Frank JA et al (2003) Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology 228(2):480–487

    Article  PubMed  Google Scholar 

  • Gambhir SS et al (2000) Imaging transgene expression with radionuclide imaging technologies. Neoplasia 2(1–2):118–138

    Article  PubMed  CAS  Google Scholar 

  • Garg M et al (2008) Radiolabeling, pharmacoscintigraphic evaluation and antiretroviral efficacy of stavudine loaded 99mTc labeled galactosylated liposomes. Eur J Pharm Sci 33(3):271–281

    Article  PubMed  CAS  Google Scholar 

  • Haacke EM et al (2004) Susceptibility weighted imaging (SWI). Magn Reson Med 52(3): 612–618

    Article  PubMed  Google Scholar 

  • Hamed IA et al (1979) Pulmonary cytomegalovirus infection: detection by Gallium 67 imaging in the transplant patient. Arch Intern Med 139(3):286–288

    Article  PubMed  CAS  Google Scholar 

  • Hayes EB, Gubler DJ (2006) West Nile virus: epidemiology and clinical features of an emerging epidemic in the United States. Annu Rev Med 57:181–194

    Article  PubMed  CAS  Google Scholar 

  • Hoehn M et al (2007) Cell tracking using magnetic resonance imaging. J Physiol 584(Pt 1):25–30

    Article  PubMed  CAS  Google Scholar 

  • Jain NK et al (2010) Biosafety level (BSL)-3 life support cell for studying live animals. Patent Application. PCT/US20100313821, filed June 16, 2010

    Google Scholar 

  • Jeha LE et al (2003) West Nile virus infection: a new acute paralytic illness. Neurology 61(1):55–59

    Article  PubMed  CAS  Google Scholar 

  • Jubeli E et al (2012) E-selectin as a target for drug delivery and molecular imaging. J Control Release 158(2):194–206

    Article  PubMed  CAS  Google Scholar 

  • Kleinschnitz C et al (2003) In vivo monitoring of macrophage infiltration in experimental ischemic brain lesions by magnetic resonance imaging. J Cereb Blood Flow Metab 23(11):1356–1361

    Article  PubMed  CAS  Google Scholar 

  • Kumar V (2005) Radiolabeled white blood cells and direct targeting of micro-organisms for infection imaging. Q J Nucl Med 49(4):325–338

    CAS  Google Scholar 

  • Kumar S et al (1997) MRI in Japanese encephalitis. Neuroradiology 39(3):180–184

    Article  PubMed  CAS  Google Scholar 

  • Kumar M et al (2010) Image-guided breast tumor therapy using a small interfering RNA nanodrug. Cancer Res 70(19):7553–7561

    Article  PubMed  CAS  Google Scholar 

  • Leyson C et al (2012) Performance comparison of ultra-ultra high resolution collimators to low-energy high resolution collimators. J Nucl Med 53(suppl 1):2409

    Google Scholar 

  • Liu N et al (2007) Radiolabeling small RNA with technetium-99m for visualizing cellular delivery and mouse biodistribution. Nucl Med Biol 34(4):399–404

    Article  PubMed  CAS  Google Scholar 

  • Liu T et al (2012) Cerebral microbleeds: burden assessment by using quantitative susceptibility mapping. Radiology 262(1):269–278

    Article  PubMed  Google Scholar 

  • Lobel U et al (2010) Three-dimensional susceptibility-weighted imaging and two-dimensional T2*-weighted gradient-echo imaging of intratumoral hemorrhages in pediatric diffuse intrinsic pontine glioma. Neuroradiology 52(12):1167–1177

    Article  PubMed  Google Scholar 

  • Luker GD, Sharma V, Piwnica-Worms D (2003) Visualizing protein-protein interactions in living animals. Methods 29(1):110–122

    Article  PubMed  CAS  Google Scholar 

  • Modo M, Hoehn M, Bulte JW (2005) Cellular MR imaging. Mol Imaging 4(3):143–164

    PubMed  Google Scholar 

  • Nahrendorf M et al (2006) Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation 114(14):1504–1511

    Article  PubMed  CAS  Google Scholar 

  • O’Connor JP et al (2007) DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents. Br J Cancer 96(2):189–195

    Article  PubMed  Google Scholar 

  • O’Connor JP et al (2008) Quantitative imaging biomarkers in the clinical development of targeted therapeutics: current and future perspectives. Lancet Oncol 9(8):766–776

    Article  PubMed  Google Scholar 

  • Padhani AR et al (2000) Dynamic contrast enhanced MRI of prostate cancer: correlation with morphology and tumour stage, histological grade and PSA. Clin Radiol 55(2):99–109

    Article  PubMed  CAS  Google Scholar 

  • Penheiter AR, Russell SJ, Carlson SK (2012) The sodium iodide symporter (NIS) as an imaging reporter for gene, viral, and cell-based therapies. Curr Gene Ther 12(1):33–47

    Article  PubMed  CAS  Google Scholar 

  • Pien HH et al (2005) Using imaging biomarkers to accelerate drug development and clinical trials. Drug Discov Today 10(4):259–266

    Article  PubMed  CAS  Google Scholar 

  • Ratai EM et al (2010) Proton magnetic resonance spectroscopy reveals neuroprotection by oral minocycline in a nonhuman primate model of accelerated NeuroAIDS. PLoS One 5(5):e10523

    Article  PubMed  Google Scholar 

  • Reinders Folmer SC et al (1986) Gallium-67 lung scintigraphy in patients with acquired immune deficiency syndrome (AIDS). Eur J Respir Dis 68(5):313–318

    PubMed  CAS  Google Scholar 

  • Richter WS (2006) Imaging biomarkers as surrogate endpoints for drug development. Eur J Nucl Med Mol Imaging 33(Suppl 1):6–10

    Article  PubMed  Google Scholar 

  • Rojas JJ, Thorne SH (2012) Theranostic potential of oncolytic vaccinia virus. Theranostics 2(4):363–373

    Article  PubMed  CAS  Google Scholar 

  • Rubin RH, Fischman AJ (1994) The use of radiolabeled nonspecific immunoglobulin in the detection of focal inflammation. Semin Nucl Med 24(2):169–179

    Article  PubMed  CAS  Google Scholar 

  • Rudin M, Weissleder R (2003) Molecular imaging in drug discovery and development. Nat Rev Drug Discov 2(2):123–131

    Article  PubMed  CAS  Google Scholar 

  • Schellingerhout D et al (1998) Mapping the in vivo distribution of herpes simplex virions. Hum Gene Ther 9(11):1543–1549

    Article  PubMed  CAS  Google Scholar 

  • Sejvar JJ et al (2003) Neurologic manifestations and outcome of West Nile virus infection. JAMA 290(4):511–515

    Article  PubMed  Google Scholar 

  • Sharma V, Luker GD, Piwnica-Worms D (2002) Molecular imaging of gene expression and protein function in vivo with PET and SPECT. J Magn Reson Imaging 16(4):336–351

    Article  PubMed  Google Scholar 

  • Shoji H et al (1994) Magnetic resonance imaging findings in Japanese encephalitis. White matter lesions. J Neuroimaging 4(4):206–211

    PubMed  CAS  Google Scholar 

  • Shu CJ et al (2010) Novel PET probes specific for deoxycytidine kinase. J Nucl Med 51(7):1092–1098

    Article  PubMed  CAS  Google Scholar 

  • Smith JJ, Sorensen AG, Thrall JH (2003) Biomarkers in imaging: realizing radiology’s future. Radiology 227(3):633–638

    Article  PubMed  Google Scholar 

  • Stoll G et al (2004) In vivo monitoring of macrophage infiltration in experimental autoimmune neuritis by magnetic resonance imaging. J Neuroimmunol 149(1–2):142–146

    Article  PubMed  CAS  Google Scholar 

  • Umenai T et al (1985) Japanese encephalitis: current worldwide status. Bull World Health Organ 63(4):625–631

    PubMed  CAS  Google Scholar 

  • US Department of Agriculture (2005) Agriculture bioterrorism protection act of 2002; possession, use and transfer of select agents and toxins, final rule. Fed Regist 70(52):13294

    Google Scholar 

  • US Department of Health and Human Services, Centers for Disease Control and Prevention, National Institutes of Health (2009) In: Chosewood LC, Wilson DE (eds) Biosafety in microbiological and biomedical laboratories, 5th edn. US Government Printing Office: Washington, DC. http://www.cdc.gov/biosafety/publications/bmbl5/. Accessed 5 Dec 2012

  • US Food and Drug Administration (2002) New drug and biological drug products; evidence needed to demonstrate effectiveness of new drugs when human efficacy studies are not ethical or feasible. Fed Regist 67(105):37988–37998

    Google Scholar 

  • Valadon P et al (2006) Screening phage display libraries for organ-specific vascular immunotargeting in vivo. Proc Natl Acad Sci USA 103(2):407–412

    Article  PubMed  CAS  Google Scholar 

  • Venneti S et al (2004) PET imaging of brain macrophages using the peripheral benzodiazepine receptor in a macaque model of neuroAIDS. J Clin Invest 113(7):981–989

    PubMed  CAS  Google Scholar 

  • Viglianti BL et al (2004) In vivo monitoring of tissue pharmacokinetics of liposome/drug using MRI: illustration of targeted delivery. Magn Reson Med 51(6):1153–1162

    Article  PubMed  CAS  Google Scholar 

  • Wanahita A et al (2007) Diagnostic sensitivity and specificity of the radionuclide (indium)-labeled leukocyte scan. J Infect 55(3):214–219

    Article  PubMed  Google Scholar 

  • Wang YX, Deng M (2010) Medical imaging in new drug clinical development. J Thorac Dis 2(4):245–252

    PubMed  Google Scholar 

  • Willmann JK et al (2008) Molecular imaging in drug development. Nat Rev Drug Discov 7(7):591–607

    Article  PubMed  CAS  Google Scholar 

  • Yarchoan R et al (1987) Response of human-immunodeficiency-virus-associated neurological disease to 3′-azido-3′-deoxythymidine. Lancet 1(8525):132–135

    Article  PubMed  CAS  Google Scholar 

  • Zimmer C et al (2004) Near-miss accident during magnetic resonance imaging by a “flying sevoflurane vaporizer” due to ferromagnetism undetectable by handheld magnet. Anesthesiology 100(5):1329–1330

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Fabian de Kok-Mercado for his contribution to this work. The content of this chapter does not necessarily reflect the views or policies of the US Department of Health and Human Services or of the institutions and companies affiliated with the authors. This work was supported by the Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases (NIAID), and Battelle Memorial Institute’s prime contract with NIAID (HHSN272200200016I).

Author information

Authors and Affiliations

  1. Integrated Research Facility, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA

    Lauren Keith Ph.D., Svetlana Chefer Ph.D., Laura Bollinger, Jeffrey Solomon Ph.D, Srikanth Yellayi B.V.Sc., Ph.D. Diplomate ACVP, Jurgen Seidel Ph.D., David Thomasson Ph.D. & Peter Jahrling Ph.D.

  2. Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Peter Jahrling Ph.D.

Authors
  1. Lauren Keith Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Svetlana Chefer Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laura Bollinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeffrey Solomon Ph.D
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Srikanth Yellayi B.V.Sc., Ph.D. Diplomate ACVP
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jurgen Seidel Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David Thomasson Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Peter Jahrling Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lauren Keith Ph.D. .

Editor information

Editors and Affiliations

  1. BRMoyer & Associates, LLC, Bedford, New Hampshire, USA

    Brian R. Moyer

  2. Covidien, Hazelwood, Missouri, USA

    Narayan P.S. Cheruvu

  3. Health and Human Services Office of the Asst Secretary of Preparedness and Response (ASPR), Biomedical Advanced Research and Development Authority (BARDA), Washington, District of Columbia, USA

    Tom C.-C. Hu

Rights and permissions

Reprints and permissions

Copyright information

© 2014 American Association of Pharmaceutical Scientists

About this chapter

Cite this chapter

Keith, L. et al. (2014). Preclinical Imaging in BSL-3 and BSL-4 Environments: Imaging Pathophysiology of Highly Pathogenic Infectious Diseases. In: Moyer, B., Cheruvu, N., Hu, TC. (eds) Pharmaco-Imaging in Drug and Biologics Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 8. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8247-5_10

Download citation

Publish with us

Policies and ethics

Search

Navigation