open access

Vol 15, Supp. C (2012)
Published online: 2013-02-19
Submitted: 2013-02-25
Accepted: 2013-02-25
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Radionuclide-based reporter gene imaging: pre-clinical and clinical implementation and application

Inna Serganova, Vladimir Ponomarev, Ronald G. Blasberg

open access

Vol 15, Supp. C (2012)
Published online: 2013-02-19
Submitted: 2013-02-25
Accepted: 2013-02-25

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-, retroand
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.

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-, retroand
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.

Get Citation

Keywords

PET, gene imaging

About this article
Title

Radionuclide-based reporter gene imaging: pre-clinical and clinical implementation and application

Journal

Nuclear Medicine Review

Issue

Vol 15, Supp. C (2012)

Pages

20-36

Published online

2013-02-19

Keywords

PET
gene imaging

Authors

Inna Serganova
Vladimir Ponomarev
Ronald G. Blasberg

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