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内容記述 |
Hyperpolarization by dynamic nuclear polarization (DNP) is a promising technique that enhances magnetic resonance signal over 10,000-fold. This allows hyperpolarized MR spectroscopy (NMR) and spectroscopic imaging (MRI) to directly probe enzymatic activity or metabolic reprogramming, including the Warburg effect2. This technique has been experimentally and clinically applied to assess therapeutic response in the early phase of cancers upon chemotherapy or radiotherapy. In this technique, bolus injection of hyperpolarized 13C-labeled molecules within a short time window (5~20 sec) is a regimen for obtaining metabolic images to maintain the hyperpolarized 13C signals for MR scan before the signals return to the thermal equilibrium levels across several tens of seconds after the injection. During such quick injection on metabolic imaging, some molecular probes have been found to induce physiological and pharmacological alterations in the tumor microenvironment. For example, pyruvate, the most promising 13C molecular probe, induces transient hypoxia by transiently increasing oxygen consumption in mitochondria, thereby decreasing tumor tissue oxygen pressure (pO2) for several hours in rodent models. Although this acute hypoxia confers resistance to X-ray irradiation in which tissue oxygenation (>10 mmHg) is necessary for tumor cell killing3, it potentiates the anti-tumor effect of hypoxia-activated prodrug evofosfamide (TH-302) that releases warhead for DNA cross-linkage under severe hypoxic regions (<10 mmHg) in tumors. In this poster, the potential of hyperpolarized magnetic resonance spectroscopic imaging in conjunction with tumor radiotherapy and chemotherapy for cancer treatment is presented as a next-generation approach for cancer medicine. In particular, direct use of hyperpolarized molecular probes for potentiating the therapeutic efficacy right after the imaging is a distinctive characteristic, which may be called “hyperpolarized MRI theranostics of cancer”. The prospects for future medical technology development brought about by hyperpolarized NMR/MRI in the field of oncology will be discussed. |
