Senior Researcher Yukie Yoshii and colleagues at the Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology have been using the copper radioisotope ⁶⁴Cu to develop a next-generation radiotherapeutic that is highly effective in treating malignant tumors and can simultaneously diagnose and treat cancer.

With the aim of implementing this next-generation radiotherapeutic into clinical practice, Senior Researcher Yoshii founded LinqMed Inc. on July 1, 2022. This venture company specializes in the development and marketing of this next-generation radiotherapeutic with the support of the Program for Creating STart ups from Advanced Research and Technology (START) by the Japan Science and Technology Agency (JST).

Among the radiotherapeutics under the development, LinqMed has initiated a Phase 3 randomized controlled clinical trial of ⁶⁴Cu-ATSM for the treatment of recurrent and refractory malignant brain tumors. This study is the final stage of clinical trials, and this agent is expected to be approved as the first-ever Japanese radiotherapeutic.

Innovative "visible" cancer radiotherapeutics with ⁶⁴Cu

Radiotherapy and chemotherapy for cancer have seen challenges including insufficient therapeutic effect and adverse reactions associated with damage to normal cells. Senior Researcher Yoshii et al. hypothesized that the copper radioisotope ⁶⁴Cu could potentially overcome these challenges and have been working to develop radiotherapeutics using ⁶⁴Cu.

In addition to the beta rays emitted by nuclides used in conventional radiotherapeutics, ⁶⁴Cu emits a specific type of radiation called Auger electrons.^*1 Auger electrons have the remarkable feature of being able to effectively treat cancer cells with high energy. Additionally, since ⁶⁴Cu also emits positrons, it can be used for positron emission tomography (PET) diagnosis. Leveraging these attributes, ⁶⁴Cu can be bound to the drug accumulating on cancer cells in order to treat the cancer while noninvasively confirming drug accumulation on the cancer (treatment with simultaneous visualization) (Fig.1).

LinqMed is committed to bringing its innovative "visible” cancer radiotherapeutics based on the distinct properties of ⁶⁴Cu to clinical practice as quickly as possible. This breakthrough has the potential to overcome refractory cancers with no effective treatment options, enable personalized therapies tailored to the condition of each patient's cancer, and optimize medical care that simultaneously assessing adverse reactions.

*1　Beta rays, Auger electrons
Beta rays generally exhibit a maximum range in the millimeter range and are used in conventional radiopharmaceuticals. Since Auger electrons generally exhibit a short maximum range in the nanometer scale, they can apply high energy in their immediate vicinity, which is generally considered to result in high therapeutic efficacy.

The first-ever first-in-human clinical trial of a radiotherapeutic developed in Japan

LinqMed has initiated a Phase 3 randomized controlled clinical trial of its investigational agent ⁶⁴Cu-ATSM as a radiotherapeutic for recurrent or refractory malignant brain tumors (Fig.2).

The treatment options have been insufficient for patients with malignant brain tumors, and further drug development has been urgently required. The hypoxic tissue microenvironment plays a key role in the poor prognosis of brain tumors. In conventional radiation therapy, radiation exposure generates reactive oxygen species (ROS), which damages the DNA of cancer cells and promotes cell death. However, hypoxia occurs in relapsed malignant brain tumors, and reduces ROS generation and making radiation therapy less effective.

To overcome these challenges, Senior Researcher Yoshii and her colleagues developed ⁶⁴Cu-ATSM, which accumulates into the hypoxic tumor cells and exhibits high therapeutic efficacy. In preclinical studies using cancer cell xenografted mice, Senior Researcher Yoshii et al. confirmed that ⁶⁴Cu-ATSM suppresses the growth of hypoxic malignant brain tumors and improves survival rates. Encouraged by these promising findings, this agent has been developed as a radiotherapeutic for malignant brain tumors. LinqMed is committed to bring this innovative technology into clinical practice as promptly as possible.

LinqMed’s commitment to innovative "visible" cancer treatment

Cancer is the leading cause of death in Japan, and the development of new diagnostic and therapeutic options is an urgent issue. LinqMed has been using the copper radioisotope ⁶⁴Cu to develop next-generation radiopharmaceuticals that can be used for both diagnostic and therapeutic purposes in cancer. We are constructing a ⁶⁴Cu GMP manufacturing site in Japan to produce ⁶⁴Cu for the Japanese market.

In addition to ⁶⁴Cu-ATSM, which targets recurrent or refractory malignant brain tumors, LinqMed is developing both diagnostic and therapeutic ⁶⁴Cu-agents for pancreatic cancer. Furthermore, several drug discovery programs targeting solid tumors, such as bile duct cancer, are underway. LinqMed is dedicated to continuously developing ⁶⁴Cu-based radiopharmaceuticals for various clinical applications and contributing to the acceleration of technological innovation in Japan.