Development

Delivering the world’s first AMPA-PET drug

What is AMPA-PET?

　AMPA receptors are one of the glutamate receptors in the brain and central nervous system, which are involved in memory and learning. It has been suggested that they are also associated with many neuropsychiatric disorders such as epilepsy, schizophrenia, depression, and bipolar disorder. However, answers to the question: “Are AMPA receptors in the brains of patients with neuropsychiatric disorders actually increasing or decreasing, and how are they distributed?” were not available to date because of the lack of technology.
Therefore, research on the correlation between diseases and AMPA receptors in humans has been slow, and the development of therapeutic agents targeting AMPA receptors has not progressed.
Under these circumstances, we have developed a special PET drug called “[¹¹C]K-2″ that can successfully visualize AMPA receptors in humans. Currently, many clinical studies involving this drug are being conducted, and the relationship between AMPA receptors and diseases is gradually becoming clear.

Application of AMPA-PET in epilepsy

　We believe that the AMPA-PET technology can be used for the diagnosis of many neuropsychiatric disorders and drug development. We are currently developing it as a focused tool for the diagnosis of epilepsy.
Epilepsy is known to affect 1 million individuals among the Japanese population alone, and approximately one-third of the patients have “refractory epilepsy”, wherein seizures cannot be easily controlled using drugs. The treatment method for patients with refractory epilepsy involves surgical removal of the brain region (focus) that causes the epilepsy. Many people with seizures have benefited from this surgery. However, to undergo this surgery, many tests are required, which take time, and put a heavy burden on the patient.
We believe that AMPA-PET allows faster and more accurate localization of the epilepsy focus when planning surgical treatment for epilepsy. We are currently conducting a phase II physician-initiated clinical trial.

AMPA-PET images of epilepsy patients. The area indicated by the white triangle is the epilepsy focal point.
*Nature Medicine* **volume 26**, pages281–288(2020)

Development of automatic synthesizer (medical device) for [¹¹C]K-2

　Since the radioisotope ¹¹C used in this PET drug has a short life (half-life of approximately 20 minutes), it is produced by a cyclotron installed in the hospital and synthesized with a compound (in-hospital production). It is then used immediately after quality inspection. Currently, we use an automatic synthesizer that is awaiting approval as a medical device in Japan. We are conducting a physician-initiated clinical trial phase II with the aim of having this synthesizer approved.

Development of [¹⁸F]K-X drug

　Many PET drugs currently in widespread use, such as FDG, are labeled with the radioactive isotope 18F. This is because ¹⁸F has a slightly longer life (half-life of approximately 110 minutes) and can be manufactured at a radiopharmaceutical manufacturer’s factory and delivered to a hospital. We are currently developing an AMPA-PET drug labeled with ¹⁸F and will begin clinical trials in the near future.

Development of AMPA receptor activating drug

　We have observed that some of the compounds related to AMPA-PET drugs can activate AMPA receptors. Currently, we are screening related compounds and aim to launch them as AMPA receptor activators.
It is possible to select target patients and determine their effects using AMPA-PE. We will make the best use of this advantage in development.