Radionuclide-based reporter gene imaging: Pre-clinical and clinical implementation and application Journal Article

Authors: Serganova, I.; Ponomarev, V.; Blasberg, R. G.
Article Title: Radionuclide-based reporter gene imaging: Pre-clinical and clinical implementation and application
Abstract: Noninvasive reporter gene imaging using radiolabeled probes was first described in 1995, and requires "pre-targeting" (delivery) of the reporter construct to the target tissue (by transfection/transduction). In each case, the reporter system involves a "complimentary pair"; a reporter gene construct and a complimentary radiolabeled probe or substrate. The most widely used reporter gene, HSV1-tk (and a variety of mutants, such as HSV1-tksr39), utilizes enzymatic amplification through phosphorylation and trapping of a specific radiolabeled probe (such as [124I]FIAU or [18F]FHBG), similar to imaging hexokinase activity with [18F]FDG. Recent attention as turned to "human" reporter genes to avoid a potential immunological response to a foreign protein; seven human reporter genes are briefly discussed. Reporter gene imaging can provide non-invasive assessments of endogenous biological processes in living subjects. At least two different reporter constructs will be required in most future applications of reporter gene imaging. One will be a "constitutive" reporter that will be used to identify the site, extent and duration of vector delivery and tissue transduction or for identifying the cell distribution/trafficking, homing/targeting and persistence (the "normalizing" or denominator term). The second one will be an "inducible" reporter that is sensitive to endogenous transcription factors, signaling pathways or protein-protein interactions that monitor the biological activity and function of the transduced cells (the "sensor" or numerator term). The initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: 1. gene therapy and 2. adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adeno-, retro- and lenteviral-based gene therapy, oncolytic bacterial and viral therapy, and adoptive cell-based therapies. The translational applications of noninvasive in vivo reporter gene imaging are likely to include: 1. quantitative monitoring of the gene therapy vector and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; 2. monitoring cell trafficking, targeting, replication and activation in adoptive T cell and stem/progenitor cell therapies; 3. assessments of endogenous molecular events using different inducible reporter gene imaging systems. Copyright © 2012 Via Medica.
Keywords: protein expression; unclassified drug; nonhuman; conference paper; nuclear magnetic resonance imaging; positron emission tomography; cell proliferation; prostate specific antigen; cell division; gene expression; protein protein interaction; clinical assessment; carcinoembryonic antigen; fluorescence; in vivo study; enzyme activity; molecular imaging; phosphorylation; imaging system; immune response; biological activity; isotope labeling; dosimetry; fluorodeoxyglucose f 18; radiopharmaceutical agent; noradrenalin transporter; oncolytic virotherapy; reporter gene; cell migration; adoptive transfer; target cell; bone marrow cell; radioisotope; single photon emission computer tomography; pet; thymidine kinase 1; cell activation; herpes simplex virus 1; bioluminescence; adoptive immunotherapy; autoradiography; heat shock transcription factor 1; gene construct; somatostatin receptor; tissue kallikrein; enhanced green fluorescent protein; deoxycytidine kinase; probasin; sodium iodide symporter; viral gene therapy; internal ribosome entry site; dopamine 2 receptor; gamma camera; good manufacturing practice; gene imaging; 9 (4 [18f] fluoro 3 hydroxymethylbutyl)guanine
Journal Title: Nuclear Medicine Review
Volume: 15
Issue: Suppl.C
ISSN: 1506-9680
Publisher: Via Medica  
Date Published: 2012-01-01
Start Page: C20
End Page: C36
Language: English
PROVIDER: scopus
Notes: --- - "Export Date: 1 August 2013" - "CODEN: NMRUA" - "Source: Scopus"
MSK Authors
  1. Ronald G Blasberg
    264 Blasberg
  2. Vladimir Ponomarev
    109 Ponomarev
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