Toward new frontiers : Encounter and synergy of state-of-the-art astronomical detectors and exotic quantum beams

Nuclear medicine is originally a non-invasive quantitative imaging technique to visualize physiological and biochemical abnormalities of human organs using small molecules such as glucose and amino acids. This clinical technique uses radiolabeled pharmaceuticals designed to accumulate in human organs of interest. Positron emission tomography (PET) provides sectional images of radioactivity distribution. Due to the recent improvement in spatial resolution, preclinical PET with small animals has become a powerful tool for development of candidate molecules for new drugs. These molecules include tumor-specific monoclonal antibodies (mAbs). Currently, small animal PET imaging is essential to evaluate mAb binding to grafted tumors in immunocompromised nude mice. By incorporating therapeutic radionuclides like α (or β) emitters with mAbs, highly tumor-specific cell damages can be achieved. Here, PET imaging can help optimize biodistribution of engineered mAb-based molecules. This emerging therapeutic technique paired with molecular diagnostic imaging (aka “theranostics”) is attracting a great deal of attention to cure cancer patients. The bombardment of α particles with high linear energy transfer (LET) can be delivered by mAbs to surface antigens of tumor cells. This results in DNA double-strand breaks, which ultimately induce apoptosis or necrosis of tumor cells. We aim at development of novel theranostic strategies for peritoneal dissemination of gastric cancer. As a therapeutic α-emitter, Astatine-211 (half-life: 7.2 hours) is a promising heavy halogen radionuclide, which can be produced by a cyclotron. However, current imaging techniques for living small animals are inadequate for visualization of ²¹¹At biodistribution, as ²¹¹At emits low energy X-rays (77–92 keV) and scarce γ-rays with high energy (570 and 898 keV, <1%). Thus, the high-resolution imaging counterpart for ²¹¹At remains a challenge to establish a one-stop shop approach for ²¹¹At theranostics. We expect that novel ²¹¹At imaging techniques will be explored by multidisciplinary collaborations, in comparison with the therapeutic outcomes after targeted radionuclide therapy of ²¹¹At as well as the conventional small animal PET images for disseminated peritoneal tumors of gastric cancer.

Fig 1. The preclinical PET scanner　(Shimadzu corporation) installed at the Isotope Science Center, the University of Tokyo.

Fig 2. A representative image of an immunocompetent mouse with peritoneal dissemination of the gastric cancer cell line YTN16.

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