Molecular imaging of cancer hypoxia and its application for internal radiotherapy targeting hypoxic microenvironment

Molecular imaging of cancer hypoxia and its application for internal radiotherapy targeting hypoxic microenvironment\nTsuneo Saga, MD, PhDMolecular Imaging Center, National Institute of Radiological Sciences (Japan)\nThe presence of hypoxia in cancers is known to increase not only their refractoriness to treatment, but also their malignant potential. The information of cancer hypoxia, therefore, is important for the management of cancer patients such as prediction of treatment response and the selection of appropriate treatment strategy. At present, two kinds of PET probes, nitroimidazole derivatives such as 18F-FMISO and 60, 62, 64Cu-ATSM, are applied for clinical evaluation of cancer hypoxia, and their usefulness in predicting treatment response and the potential applicability for radiation treatment planning has been reported. We have conducted clinical studies using 18F-FAZA, 2nd generation nitroimidazole probe, for lung cancer and head and neck cancer patients receiving chemoradiotherapy, and evaluated the relationship of 18F-FAZA uptake and treatment response and survival of the patients. Clinical studies using 62Cu-ATSM, which accumulates in hypoxic tissue by different mechanism from that of nitroimidazoles, is also ongoing in several institutions in Japan, showing promising results. Our basic studies have shown that the intratumoral area showing high Cu-ATSM uptake constructs cancer stem cell-rich region. We, then, evaluated the potential of Cu-ATSM labeled with 64Cu, which emits -rays and Auger electrons in addition to positrons, as an internal radiotherapy (IRT) probe targeting hypoxic microenvironment. Experimental IRT study in mouse model has shown that the administration of high dose of 64Cu-ATSM showed significant therapeutic effect and reduced the number of cancer stem cells. For the safe clinical application, high physiological uptake of 64Cu-ATSM in the liver should be reduced, and we developed a method to reduce high physiological uptake in the liver.In this symposium, I would like to briefly summarize clinical results of hypoxia PET and also our preclinical evaluations aiming for the development of IRT targeting hypoxic microenvironment.15th International Congress of Radiation Research(ICRR2015