Radionuclide therapy is one of the fields of nuclear medicine and it uses a tumor-specific antibody or peptide that labeled with charged-particle（α particle, β^－particle, Auger electron) emitted radionuclide for treatment of tumors. Among those radiations, α particle has been paid attention to clinical application owing to its short path length in tissue and high liner-energy-transfer (LET). There are several promising alpha-emitting radionuclides such as ²¹¹At, ²¹²Bi, ²¹²Pb, ²²³Ra, ²²⁷Th, ²¹³Bi and ²²⁵Ac. Among them, ²²⁵Ac labeled peptide, ²²⁵Ac-PSMA-617 has shown the most encouraging outcomes including complete remission of metastasized prostate cancer of patients. However, in order to understand the therapeutic effect of the ²²⁵Ac which acts as an in vivo generator and applies to the other cancer treatment, we need to know the physical and chemical properties of the parent and its daughter nuclides to control in vivo.

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We are developing production technologies of radioisotopes（RIs）for application studies using heavy-ion accelerators at RIKEN RI Beam Factory (RIBF). More than 100 RIs produced at the AVF cyclotron, RIKEN Linear Accelerator, and RIKEN Ring Cyclotron have been used in research fields of physics, chemistry, biology, engineering, medicine, pharmaceutical and environmental sciences. In this article, production technologies of cupper-67 and astatin-211 for future targeted radionuclide therapy are presented. Among RIKEN RIs, purified RIs such as zinc-65 and cadmium-109 are delivered to universities and institutes through Japan Radioisotope Association. Short-lived RIs are also distributed to researchers through the platform for short-lived RI distribution supported by KAKENHI.

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α-Emitters show higher cytocidal effects compared with β-emitters because α-emitters can deposit high energy within a short range, whereas the range of β-emitters is longer. Although α-radioimmunotherapy (α-RIT), a therapeutic nuclear medicine with radiolabeled antibodies with α-emitters, has the potential of high therapeutic efficacy; many clinical trials for hematological malignancies have been done, but a few for solid tumors. However, the clinical trials are increasing and four trials with ²²⁵Ac and ²²⁷Th, which would play a major role in nuclear medicine for solid tumors, started in 2017 or later. Research and development of different α-RIT is conducted over the world. In this section, we first provide an overview of RIT and then focus on α-RIT.

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Boron neutron capture therapy（BNCT） has been attracting growing interest as one of the minimally invasive cancer therapies. BNCT uses the nuclear reaction between low-energy thermal neutron（0.025eV） and boron-10（¹⁰B）, and the generated α-particle and lithium nuclei are high linear energy transfer particles（2.4MeV） that are sufficiently powerful to kill cells. Therefore, selective delivery of ¹⁰B atoms to tumor is essential for effective BNCT. Mercaptoundecahydrododecaborate（Na₂［B₁₂H₁₁SH］） and p-boronophenylalanine（BPA） have been used in BNCT for many years. BPA, in particular, has been widely used for the treatment of not only melanoma but also brain tumor and head and neck cancer. In Japan, which succeeded in developing a small accelerator for BNCT ahead of the world, the phase II clinical study of BPA-BNCT for brain tumor and head and neck cancer patients has been completed and their applications for medical approval have been filed. However, development of new boron carriers is still strong requirements for patients who are not able to be treated with BPA. In this review, recent development of DDS-based new boron carriers is summarized.

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Neutron capture therapy（NCT）, a type of radiation therapy for cancer, utilizes radiation emitted as a result of the reaction between neutron capture elements, such as boron（¹⁰B）and gadolinium（¹⁵⁷Gd）, located in the tumor and thermal neutrons irradiated from outside the body. In NCT with ¹⁰B（BNCT）, the homogeneous distribution of ¹⁰B in tumor tissues contributes to cancer treatment by selectively generating alpha rays in or near tumor cells, thereby destroying individual tumor cells in a brief irradiation session, without affecting surrounding normal tissues. With the success of a small-typed accelerator with NCT development and its setup in hospitals, NCT as a treatment for cancer will expand its potential and indications. In this report, an overview of current status of NCT in clinical studies is given. Then, our preclinical studies on the cellular uptake behavior and biodistribution of ¹⁰B and anti-tumor effects in treating soft tissue sarcoma by BNCT are described. In addition, the potential of a gadolinium formula as a new pharmaceutical agent with NCT is also discussed.

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