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Early gene therapy–induced apoptotic response in BT4C gliomas by magnetic resonance relaxation contrast T1 in the rotating frame

Cancer Gene Therapy volume 9, pages 338–345 (2002)Cite this article

Abstract

The design and evaluation of therapeutic gene transfection protocols and vectors are under extensive development. Magnetic resonance imaging (MRI) techniques can aid considerably in the development of experimental treatment approaches, as well as in determining treatment response by observing gross tissue morphology. However, through a unique set of contrast parameters, namely T1, T2, and diffusion, more information about tissue status can be obtained while delineating and classifying tumor characteristics in more detail. We show here that T1 relaxation in the rotating frame, T1ρ, provides unique in vivo MRI contrast. Ganciclovir treatment of HSV-tk+BT4C gliomas, which effectively eradicates these tumors, resulted in significantly prolonged T1ρ relaxation times in MRI already after 3 days of treatment, whereas conventional contrast parameters were elevated after 6–8 days of therapy. Interestingly, the prolonged T1ρ values were observed while an increase in tumor volume was still taking place. The regions of elevated T1ρ relaxation coincided with high apoptotic activity as determined by histology, suggesting that T1ρ MRI contrast could be used as a novel early indicator of cytotoxic cell damage in gliomas.

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Acknowledgements

This study was supported by the Academy of Finland, The Finnish Cancer Societies, Sigrid Juselius Foundation, and Emil Aaltonen Foundation. Technical assistance by Ms Nina Kuhmonen and Ms Mervi Riekkinen is gratefully acknowledged.

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Authors and Affiliations

  1. National Bio-NMR Facility, AI Virtanen Institute for Molecular Sciences, University Hospital of Kuopio, Kuopio, FIN-70211, Finland

    Juhana M Hakumäki, Olli H J Gröhn, Piia Valonen & Risto A Kauppinen

  2. Molecular Medicine Laboratory, AI Virtanen Institute for Molecular Sciences, University Hospital of Kuopio, Kuopio, FIN-70211, Finland

    Kristiina Tyynelä & Seppo Ylä-Herttuala

  3. Gene Therapy Unit, University Hospital of Kuopio, Kuopio, FIN-70211, Finland

    Kristiina Tyynelä & Seppo Ylä-Herttuala

Authors
  1. Juhana M Hakumäki
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  2. Olli H J Gröhn
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  3. Kristiina Tyynelä
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  4. Piia Valonen
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  6. Risto A Kauppinen
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Correspondence to Risto A Kauppinen.

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Hakumäki, J., Gröhn, O., Tyynelä, K. et al. Early gene therapy–induced apoptotic response in BT4C gliomas by magnetic resonance relaxation contrast T1 in the rotating frame. Cancer Gene Ther 9, 338–345 (2002). https://doi.org/10.1038/sj.cgt.7700450

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