Hiroki Matsumoto, Ph.D.

The University of Tokyo, Isotope Science Center, Project Professor

Showa Medical University, School of Pharmaceutical Sciences, Visiting Professor

National Cancer Center Hospital, Department of Diagnostic Radiology, Visiting Researcher

First-class Radiation Protection Supervisor

Areas of expertise : Radiopharmaceutical Sciences

On January 1, 2024, I was appointed as a Project Professor in the newly established Social Cooperation Division at the University of Tokyo Isotope Science Center. Our research focuses on the development of pharmaceuticals that harness the unique properties of radioisotopes (RIs)^*1. By accelerating the social implementation of innovative RI-based drugs, we strive to contribute to overcoming cancer and other refractory diseases.

1. RI-based Drug Discovery

Our research focuses on drug discovery aimed at providing new therapeutic options for refractory diseases, where current treatment methods offer only limited effectiveness. By leveraging the unique properties of radioisotopes (RIs), we design drugs that precisely deliver RIs to target the molecular and cellular characteristics of these diseases. Using disease model animals, we investigate the mechanisms of action to ensure the efficacy and safety of these novel treat options.

2. Preclinical & Translational Research

For promising RI-based drug candidates identified through drug discovery research, we evaluate their safety and efficacy using animal models and cell-based assays towards clinical trials. We carefully design appropriate preclinical studies by considering key clinical trial parameters, such as target patient populations, administration routes, and dosage levels. Additionally, it is crucial to assess internal radiation exposure based on the pharmacokinetics of RI-based drug candidates. To ensure their safe administration in clinical trials, we also develop manufacturing and quality control methods in compliance with Good Manufacturing Practice (GMP) for investigational drugs^*2.

3. Clinical Research Support Programs

The clinical trials for RI-based drug candidates have unique characteristics that set them apart from those for conventional pharmaceuticals.
One key challenge is that RI-based investigational drugs cannot be stored due to the radioactive decay^*6 of the isotopes. As a result, they must be frequently manufactured in small batches for each administration day. To address this, we collaborate with GMP-compliant facilities for investigational drugs to ensure proper manufacturing and quality control procedures dedicated to RI-based pharmaceuticals.
Additionally, the pharmacokinetic analysis and metabolite profiling of RI-based investigational drugs require specialized methodologies different from those used for conventional drugs. Evaluating internal radiation exposure is also a critical aspect specific to RI-based therapies. Our team actively supports clinical trial sites in these specialized areas, ensuring that RI-based drug candidates are developed safely and effectively.

Glossary

^*1 Radioisotopes (RIs): Isotopes are atoms of the same element that share identical chemical properties but have slightly different atomic masses. Among these, those that emit radiation are known as radioisotopes (RIs).

^*2GMP for investigational drugs refers to the appropriate manufacturing and quality control procedures, as well as the required structural and facility standards, that must be followed when producing investigational drugs. These guidelines were issued by the Director-General of the Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare (MHLW), in Notification No. 0709002 on July 9, 2008, outlining the standards for the manufacturing and quality control of investigational drugs.

^*3PMDA: The Pharmaceuticals and Medical Devices Agency. PMDA is an independent administrative organization responsible for reviewing and approving the quality, efficacy, and safety of pharmaceuticals, medical devices, and regenerative medicine products in Japan.

^*4Regulatory Science (RS) Strategy Consultations are advisory services provided by the PMDA, primarily for universities, research institutions, and venture companies. These consultations offer guidance on the selection of drug candidates and the planning of necessary studies and clinical trials, particularly from the final stages of candidate selection through the early phases of clinical development.

^*5 Core Clinical Research Hospitals are medical institutions designated under Japan’s Medical Care Act to play a central role in promoting the development of innovative pharmaceuticals and medical technologies originating in Japan. These hospitals are officially designated by the Minister of Health, Labour and Welfare.

^*6Decay: Radioisotopes (RIs) gradually lose their radioactivity over time, a process known as decay. The time required for radioactivity to decrease to half of its original level is called the half-life or physical half-life. The half-life varies depending on the type of RI, but most RIs used in medical applications have half-lives ranging from a few hours to several days.

Publications (peer-reviewed)

Drug Discovery

1. ⁶⁴Cu²⁺ Complexes of Tripodal Amine Ligands’ In Vivo Tumor and Liver Uptakes and Intracellular Cu Distribution in the Extrahepatic Bile Duct Carcinoma Cell Line TFK-1: A Basic Comparative Study. Shinada, M.; Takahashi, M.; Igarashi, C.; Matsumoto, H.; Hihara, F.; Tachibana, T.; Oikawa, M.; Suzuki, H.; Zhang, M.-R.; Yoshii, Y.; et al. Pharmaceuticals 2024, 17, 820.
2. Trace Metal Impurities Effects on the Formation of [⁶⁴Cu]Cu-diacetyl-bis(N⁴-methylthiosemicarbazone) ([⁶⁴Cu]Cu-ATSM). Shinada, M.; Suzuki, H.; Hanyu, M.; Igarashi, C.; Matsumoto, H.; Takahashi, M.; Hihara, F.; Tachibana, T.; Sogawa, C.; Zhang, M.-R.; Higashi, T.; Sato, H.; Kurihara, H.; Yoshii, Y.; Doi, Y. Pharmaceuticals 2024, 17, 10.
3. An In Vivo Dual-Observation Method to Monitor Tumor Mass and Tumor-Surface Blood Vessels for Developing Anti-Angiogenesis Agents against Submillimeter Tumors. Tachibana, T.; Oyama, T.G.; Yoshii, Y.; Hihara, F.; Igarashi, C.; Shinada, M.; Matsumoto, H.; Higashi, T.; Kishimoto, T.; Taguchi, M. Int. J. Mol. Sci. 2023, 24, 17234.
4. In Vitro Tumor Cell-Binding Assay to Select High-Binding Antibody and Predict Therapy Response for Personalized ⁶⁴Cu-Intraperitoneal Radioimmunotherapy against Peritoneal Dissemination of Pancreatic Cancer: A Feasibility Study. Hihara, F.; Matsumoto, H.; Yoshimoto, M.; Masuko, T.; Endo, Y.; Igarashi, C.; Tachibana, T.; Shinada, M.; Zhang, M.-R.; Kurosawa, G.; et al. Int. J. Mol. Sci. 2022, 23, 5807.
5. Efficacy of vorinostat-sensitized intraperitoneal radioimmunotherapy with ⁶⁴Cu-labeled cetuximab against peritoneal dissemination of gastric cancer in a mouse model. Tachibana T, Yoshii Y, Matsumoto H, Higashi T, et al. J Cancer Res Ther. 2022 Jul-Sep;18(4):907-914.
6. Usefulness of PET-guided surgery with ⁶⁴Cu-labeled cetuximab for resection of intrapancreatic residual tumors in a xenograft mouse model of resectable pancreatic cancer. Igarashi C, Yoshii, Y, Matsumoto H, et al. Nuclear Medicine Communications 42(10):p 1112-1121, October 2021.
7. Immuno-OpenPET: a novel approach for early diagnosis and image-guided surgery for small resectable pancreatic cancer. Yoshii Y, Matsumoto H, Higashi T, et al. Sci Rep 2020, 10, 4143.
8. Comparative evaluation of [¹⁸F]DiFA and its analogs as novel hypoxia positron emission tomography and [¹⁸F]FMISO as the standard. Nakata N, Kiriu M, Okumura Y, Zhao S, Nishijima KI, Shiga T, Tamaki N, Kuge Y, Matsumoto H. Nucl Med Biol. 2019;70:39-45
9. ⁶⁴Cu-intraperitoneal radioimmunotherapy: a novel approach for adjuvant treatment in a clinically relevant preclinical model of pancreatic cancer. Yoshii Y, Matsumoto H, Yoshimoto M, Oe Y, Zhang MR, Nagatsu K, Sugyo A, Tsuji AB, Higashi T. J Nucl Med. 2019 doi: 10.2967/jnumed.118.225045.
10. Biodistribution and radiation dosimetry of the novel hypoxia PET probe [¹⁸F]DiFA and comparison with [¹⁸F]FMISO. Watanabe S, Shiga T, Hirata K, Magota K, Okamoto S, Toyonaga T, Higashikawa K, Yasui H, Kobayashi J, Nishijima KI, Iseki K, Matsumoto H, Kuge Y, Tamaki N. EJNMMI Res. 2019:5;9(1):60
11. A Novel PET Probe "[¹⁸F]DiFA" Accumulates in Hypoxic Region via Glutathione Conjugation Following Reductive Metabolism. Shimizu Y, Matsumoto H, et al., Mol Imaging Biol 2019;21(1):122-129.
12. Design, Synthesis, and Preliminary Evaluation of SPECT Probes for Imaging β-Amyloid in Alzheimer's Disease Affected Brain. Okumura Y, Matsumoto H, et al., ACS Chem Neurosci. 2018;9(6):1503-1514.
13. Integrated treatment using intraperitoneal radioimmunotherapy and positron emission tomography-guided surgery with ⁶⁴Cu-labeled cetuximab to treat early- and late-phase peritoneal dissemination in human gastrointestinal cancer xenografts. Yoshii Y, Matsumoto H, et al., Oncotarget. 2018:9(48); 28935- 28950.
14. ⁶⁴Cu-ATSM internal radiotherapy to treat tumors with bevacizumab-induced vascular decrease and hypoxia in human colon carcinoma xenografts. Yoshii Y, Matsumoto H, et al., Oncotarget. 2017 28;8(51): 88815-88826.
15. The Thymidine Phosphorylase Imaging Agent ¹²³I-IIMU Predicts the Efficacy of Capecitabine. Kobashi N, Matsumoto H, Kuge Y et al., J Nucl Med 2016; 57:1276–1281.
16. A novel CYP11B2-specific imaging agent for detection of unilateral subtypes of primary aldosteronism. Abe T, Naruse M, Matsumoto H et al. J Clin Endocrinol Metab. 2016, 101(3):1008–1015
17. ⁶⁴Cu-ATSM therapy targets regions with activated DNA repair and enrichment of CD133+ cells in an HT-29 tumor model: Sensitization with a nucleic acid antimetabolite. Yoshii Y, Furukawa T, Matsumoto H, et al. Cancer Letters 2016;376:74–82.
18. Evaluation of trans-1-amino-3-¹⁸F-fluorocyclobutanecarboxylic acid accumulation in low-grade glioma in chemically induced rat models: PET and autoradiography compared with morphological images and histopathological findings. Doi Y, Kanagawa M, Matsumoto H et al. Nucl Med Biol. 2015, 42:664-672.
19. Controlled administration of penicillamine reduces radiation exposure in critical organs during ⁶⁴Cu-ATSM internal radiotherapy: a novel strategy for liver protection. Yoshii Y, Matsumoto H, Sogawa C, et al., PLoS ONE 2014;9(1):e86996

Preclinical & Translational Research

1. Process to Remove the Size Variants Contained in the Antibody–Chelator Complex PCTA-NCAB001 for Radiolabeling with Copper-64. Yoshii, Y.; Matsumoto, H.; Igarashi, C.; Tachibana, T.; Hihara, F.; Shinada, M.; Waki, A.; Yoshida, S.; Naito, K.; Ito, K.; Higashi, T.; Kurihara H.; Ueno M. Pharmaceuticals 2023, 16, 1341. doi:10.3390/ph16101341
2. Preclinical Safety Evaluation of Intraperitoneally Administered Cu-Conjugated Anti-EGFR Antibody NCAB001 for the Early Diagnosis of Pancreatic Cancer Using PET. Matsumoto, H.; Igarashi, C.; Tachibana, T.; Hihara, F.; Shinada, M.; Waki, A.; Yoshida, S.; Naito, K.; Kurihara, H.; Ueno, M.; et al. Pharmaceutics 2022, 14, 1928.
3. Characterization and Stabilization of a New ⁶⁴Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography. Matsumoto, H.; Igarashi, C.; Tachibana, T.; Hihara, F.; Waki, A.; Zhang, M.-R.; Yoshida, S.; Naito, K.; Kurihara, H.; Ueno, M.; et al. Pharmaceutics 2022, 14, 67.
4. Identification and quantitative structure–activity relationship assessment of trace chemical impurities contained in the therapeutic formulation of [⁶⁴Cu]Cu-ATSM. Igarashi C, Matsumoto H, Yoshii Y, et al. Nuclear Medicine and Biology. 2022.108–109: 10-15.
5. Evaluation of ⁶⁴Cu-labeled new anti-EGFR antibody NCAB001 with intraperitoneal injection for early PET diagnosis of pancreatic cancer in orthotopic tumor-xenografted mice and nonhuman primates. Matsumoto, H.; Watabe, T.; Igarashi, C.; Tachibana, T.; Hihara, F.; Waki, A.; Zhang, M.-R.; Tashima, H.; Yamaya, T.; Ooe, K.; et al. Pharmaceuticals 2021, 14, 950.
6. Process development of [⁶⁴Cu]Cu-ATSM: efficient stabilization and sterilization for therapeutic applications. Matsumoto H, Igarashi C, Kaneko E, Hashimoto H, Suzuki H, Kawamura K, Zhang M-R, Higashi T, Yoshii Y. J Radioanal Nucl Chem 2019;322:467-475.
7. Preclinical pharmacokinetic and safety studies of copper-diacetyl-bis(N⁴- methylthiosemicarbazone) (Cu-ATSM): translational studies for internal radiotherapy. Matsumoto H, Yoshii Y, Baden A, Kaneko E, Hashimoto H, Suzuki H, Kawamura K, Zhang M-R, Higashi T, Kurihara H. Transl Oncol 2019;12:1206-1212.
8. Multiple Administrations of ⁶⁴Cu-ATSM as a Novel Therapeutic Option for Glioblastoma: a Translational Study Using Mice with Xenografts. Yoshii Y, Matsumoto H, et al., Transl Oncol. 2018;11(1):24-30.

Clinical Research

1. Phase I clinical trial of ⁶⁴Cu-ATSM for malignant brain tumors. Kurihara H, Narita Y, Matsumoto H, et al. J Clin Oncol 42, 2024 (suppl 16; abstr 2052)
2. Measurement of Airborne Radioactivity in the Inpatient Room after Administering [⁶⁴Cu]Cu-ATSM to Patients. Ito K, Kurihara H, Matsumoto H, et al., Kakuigaku (Jpn J Nucl Med) 2025, 62(1), 1-6.

Competitive Research Funding Involved

Japan Agency for Medical Research and Development (AMED)

Project Promoting Clinical Trials for Development of New Drugs (FY2022–FY2025)

"Phase I Physician-Initiated Clinical Trial of Innovative PET Imaging Using Endoscopic Ultrasound-Guided Administration of Novel Radioactive Antibody Drugs for Early Detection and Precision Treatment of Pancreatic Cancer" (Research Collaborator)

Project Promoting Clinical Trials for Development of New Drugs (FY2023–FY2026)

"Research and Development to Evaluate the Efficacy of the Therapeutic Radioactive Agent ⁶⁴Cu-ATSM for Recurrent and Refractory Malignant Gliomas" (Research Collaborator)

Japan Science and Technology Agency (JST)

Program for Creating Startups from Advanced Research and Technology (FY2020–FY2022)

"Technological Development for Commercialization of Innovative Radioactive Cancer Therapeutics" (Research Collaborator)