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Imaging
in Gene Therapy of Patients with Glioma
A.H.
Jacobs, J.
Voges, L.W.
Kracht, C.
Dittmar, A.
Winkeler, A.
Thomas, K.
Wienhard, K.
Herholz, W.D.
Heiss
Max
Planck-Institute for Neurological Research, Center of Molecular Medicine (ZMMK),
Department of Neurology, University of Cologne, Cologne, Germany
Over 10
years ago, the first successful gene therapy paradigms for experimental brain
tumors models have been conducted, and they were thought to revolutionize the
treatment of patients with gliomas.
Application of gene therapy has been quickly forced into clinical trials, the
first patients being enrolled in 1994, with overall results being
disappointing.
However, single patients seemed to benefit from gene therapy showing long-term
treatment response, and most of these patients bearing small
glioblastomas.
Whereas the gene therapy itself has been performed with high sophistication,
limited attention has been paid on technologies, which
(i) allow an identification of viable target tissue in heterogenous glioma
tissue and which
(ii) enable an assessment of successful vector administration and
vector-mediated gene expression in vivo.
However, these measures are a prerequisite for the development of successful
gene therapy in the clinical application.
As biological treatment strategies such as gene and cell-based therapies hold
promise to selectively correct disease pathogenesis, successful clinical
implementation of these treatment strategies rely on the establishment of
molecular imaging technology allowing the non-invasive assessment of endogenous
and exogenous gene expression in vivo.
Imaging endogenous gene
expression will allow the characterization and identification of target tissue
for gene therapy.
Imaging exogenously introduced cells and genes will allow the
determination of the 'tissue dose' of transduced cell function and
vector-mediated gene expression, which in turn can be correlated to the induced
therapeutic effect.
Only these combined strategies of non-invasive imaging of
gene expression in vivo will enable the establishment of safe and
efficient vector administration and gene therapy protocols for clinical
application.
Here, we review some aspects of imaging in gene therapy trials for
glioblastoma, and we present a 'proof-of-principle' 2nd-generation gene therapy
protocol integrating molecular imaging technology for the establishment of
efficient gene therapy in clinical application.
Keywords:
FHBG,
FIAU, functional imaging, gene therapy, glioblastoma, HSV-1 thymidine kinase,
molecular imaging
Copyright
©
2003 Kluwer Academic Publishers.
All
rights reserved
Source: http://ipsapp009.kluweronline.com/content/getfile/5042/105/11/abstract.htm
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