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

Juhana M. Hakumäki, Olli H J Gröhn, Kristiina Tyynelä, Piia Valonen, Seppo Ylä-Herttuala, Risto A. Kauppinen

    Research output: Contribution to journalArticlepeer-review

    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, T1p, provides unique in vivo MRI contrast. Ganciclovir treatment of HSV-tk+BT4C gliomas, which effectively eradicates these tumors, resulted in significantly prolonged T1p 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 T1p values were observed while an increase in tumor volume was still taking place. The regions of elevated T1p relaxation coincided with high apoptotic activity as determined by histology, suggesting that T1p MRI contrast could be used as a novel early indicator of cytotoxic cell damage in gliomas.
    Original languageEnglish
    Pages (from-to)338-345
    Number of pages7
    JournalCancer Gene Therapy
    Volume9
    Issue number4
    DOIs
    Publication statusPublished - 2002

    Keywords

    • Apoptosis
    • Glioma
    • HSV-tk
    • Magnetic resonance
    • Magnetic resonance imaging
    • Relaxation

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