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  • Improved treatment of malignant glioma with clinical use of a Newly Developed PET Molecular Imaging Probe [methyl-11c]-4`-thiothimidine (4DST) to measure DNA synthesis rate.

    Final Number:

    Tadashi Nariai MD PhD; Motoki Inaji MD; Shihori Hayashi MD; Yoji Tanaka; Taketoshi Maehara MD, PhD; Kiichi Ishiwata PhD; Jun Toyohara

    Study Design:
    Clinical Trial

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2013 Annual Meeting

    Introduction: PET molecular imaging is now known as an inevitable clinical tool for the treatment of malignant brain tumors. PET amino acid probes such as 11C-methionine (MET) are considered as one of most appropriate probes for clinical use. MET-PET, however, is not almighty and has several cautious points. It may over-estimates tumor malignancy in oligodendroglioma, because of the influence of vascular bed. It may not clearly differentiate low grade tumor and inflammatory disease. Recently we developed [methyl-11C]4`-thiothimidine (4DST) as a radiotracer for DNA synthesis. We evaluated the utility of 4DST-PET in comparison to MET-PET.

    Methods: 56 patients were enrolled in this study; 48 patients with glioma, 5 metastatic brain tumor, 1 malignant lymphoma, mutiple sclerosis, and craniopharyngioma. All subjects underwent 4DST and MET-PET within a week. Regional uptake of tracers in static condition (40-60 min and 20-25 min after injection for 4DST and MET, respectively) was expressed as tumor/normal ratio for MET, and SUV in 4DST-PET.

    Results: 1) 4DST-PET images were almost identical to MET-PET images in astrocytic tumors before treatments. This result suggested the validity of 4DST-PET in preoperative diagnosis of astrocytic tumors. Threshold of malignancy is 1.0 (SUV) in 4DST-PET images. 4DST-PET could distinguish between oligodendroglioma and anaplastic oligodendroglioma clearly. Furthermore, 4DST uptake was far less than 1.0 (SUV) in a case of multiple sclerosis. These results suggested that 4DST-PET image showed cell proliferation precisely and could complement the area that cannot be clarified with MET-PET. 2) The effectiveness of radiation or chemotherapy was clearly demonstrated by the decreased uptake of 4DST, instantly after the treatment.

    Conclusions: The utility and validity of 4DST-PET were demonstrated in our initial clinical trial for malignant brain tumors. As 4DST-PET may reflect cell proliferation rates more clearly than MET-PET, it has great potential as a PET molecular imaging probe for the management of malignant brain tumors.

    Patient Care: We may be able to differentiate tumor type before the operation more precisely, and to monitor the effectiveness and limitation of each treatment promptly by new imaging method.

    Learning Objectives: to learn how a newly developed molecular imaging contribute to the treatment of malignant glioma.

    References: 1. Toyohara J, Nariai T, Sakata M, Oda K, Ishii K, Kawabe T, Irie T, Saga T, Kubota K, Ishiwata K. Whole-Body Distribution and Brain Tumor Imaging with 11C-4DST: A Pilot Study. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2011 Aug;52(8):1322-8. 2. Nariai T, Inaji M, Sakata M, Toyohara J. Use of (11)C-4DST-PET for Imaging Human Brain Tumors. In: Hayat M, editor. Tumors of the central nervous system. Amsterdam: Springer; in press.

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