Annual Report 2022
Division of Functional Imaging
Anri Inaki, Hirohumi Fujii, Masayuki Yamaguchi, Mitsuyoshi Yoshimoto, Kazunobu Ohnuki, Chikayo Ide, Mizuki Akatsuka, Hiroaki Sagara, Yoko Suzuki
Introduction
Our division is actively investigating imaging technologies to visualize the functional aspects of tumor lesions to establish minimally invasive individualized therapeutic strategies. We are particularly engaged in nuclear medicine tests, magnetic resonance imaging (MRI) tests, optical imaging tests and their fusion methods, using the most advanced imaging devices equipped in our division.
The Team and What We Do
Continuing from the previous year, we conducted molecular imaging research this year as well, focusing on nuclear medicine, optical imaging, and MRI to advance noninvasive and optimized approaches to cancer treatment.
Research Activities
In the field of nuclear medicine, we have advanced non-clinical research using the alpha-emitting radionuclides At-211 and Ac-225. In experimental cancer treatment using At-211-labeled antibodies, we confirmed improved therapeutic outcomes in At-211-labeled antibody therapy by preventing antibody destruction using a radical scavenger. In addition, regarding At-211, we experimentally verified that a polyethylene filter paper, previously used for contamination prevention in unsealed radioisotope experiments, is ineffective, sounding a warning to users.
In experimental cancer treatment using Ac-225-labeled peptides, we confirmed the need for high-quality Ac-225 to achieve satisfactory therapeutic outcomes. Concurrently, in collaboration with industry partners, we have progressed in the development of technology using electron beams from accelerators to manufacture Ac-225 with minimal isotope contamination.
To operationalize dose assessment in alpha-ray therapy, we also conducted investigations into high-performance semiconductor gamma cameras for in vivo imaging of alpha-emitting radionuclides.
In the field of MRI, we developed a novel cluster analysis technique for the quantitative evaluation of MRI images to assess the pharmacological effects of new anticancer agents. This allowed us to objectively demonstrate the therapeutic effects of anticancer agents that not only destroy cancer cells but also improve cancer microcirculation, indicating new pharmacological effects. Additionally, in MRI, by placing the receiving coil in close proximity to the target organ under evaluation, excellent spatial resolution was achieved. We successfully developed a small coil targeting small organs such as the testes, and successfully depicted structures believed to be seminiferous tubules within the testes.
In the field of molecular imaging, lesions were observed using long-wavelength near-infrared fluorescence, and its application to endoscopy and other techniques is being advanced. However, challenges remain for deep tissue imaging and quantitative assessment. To address these issues, we have been developing novel molecular probes by combining near-infrared fluorescent agents with superparamagnetic materials. This study aims to observe lesions using two imaging modalities, optical imaging, and MRI, addressing the limitations associated with deep tissue imaging and quantitative evaluation.
Education
Research guidance, including animal experiments, has been provided to graduate students specializing in medicine, radiological technology, and engineering, as well as to physicians and students from other universities.
Future Prospects
Due to the reliance on nearly 100% imports of radioactive isotopes used in nuclear medicine diagnosis and treatment, we are progressing with technical verification for domestic production. We also aim to develop devices that contribute to the widespread adoption of nuclear medicine treatments.
List of papers published in 2022
Journal
1. Yamaguchi M, Kojo K, Akatsuka M, Haishi T, Kobayashi T, Nakajima T, Nishiyama H, Fujii H. High Resolution MR Imaging of the Testis Using a Small Radiofrequency Coil. Magnetic resonance in medical sciences, 22:127-136, 2023
2. Wakabayashi H, Mori H, Hiromasa T, Akatani N, Inaki A, Kozaka T, Kitamura Y, Ogawa K, Kinuya S, Taki J. (125)I-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol ((125)I-OI5V) imaging visualized augmented sigma-1 receptor expression according to the severity of myocardial ischemia. Journal of nuclear cardiology, 30:653-661, 2023
3. Akatani N, Wakabayashi H, Kayano D, Inaki A, Takata A, Hiromasa T, Yamase T, Kunita Y, Watanabe S, Mori H, Saito S, Nakajima K, Kinuya S. Long-term outcomes and prognostic factors of patients with lung metastases from differentiated thyroid cancer after radioiodine therapy in Japan. Endocrine journal, 70:315-322, 2023
4. Komatsu M, Kinoshita T, Akimoto E, Yoshida M, Terajima D, Nagata H, Habu T, Okayama T, Takabe Y, Harada J, Yamaguchi M, Yura M. The Significance of Staging Laparoscopy in Detection of Radiologically Occult Peritoneal Carcinomatosis in Gastric Cancer With Gastric Outlet Obstruction: Consideration of The Optimal Treatment Approach. Anticancer research, 42:5571-5578, 2022
5. Suzuki H, Mitsunaga S, Ikeda M, Aoyama T, Yoshizawa K, Yamaguchi M, Suzuki M, Narita M, Kawasaki T, Ochiai A. Interleukin 6/gp130 axis promotes neural invasion in pancreatic cancer. Cancer medicine, 11:5001-5012, 2022
6. Nakagawa M, Yamaguchi M, Endo M, Machida Y, Hattori A, Tanzawa F, Tsutsumi S, Kitabayashi I, Kawai A, Nakatani F. Clinical usefulness of 2-hydroxyglutarate as a biomarker in IDH-mutant chondrosarcoma. Journal of bone oncology, 34:100430, 2022
7. Ohnuki K, Yoshimoto M, Haba H, Manabe S, Takashima H, Yasunaga M, Takenaka Y, Fujii H. Protection from contamination by (211)At, an enigmatic but promising alpha-particle-emitting radionuclide. EJNMMI physics, 9:39, 2022
8. Kuroda R, Wakabayashi H, Araki R, Inaki A, Nishimura R, Ikawa Y, Yoshimura K, Murayama T, Imai Y, Funasaka T, Wada T, Kinuya S. Phase I/II clinical trial of high-dose [(131)I] meta-iodobenzylguanidine therapy for high-risk neuroblastoma preceding single myeloablative chemotherapy and haematopoietic stem cell transplantation. European journal of nuclear medicine and molecular imaging, 49:1574-1583, 2022
9. Wakabayashi H, Inaki A, Yoshimura K, Murayama T, Imai Y, Higuchi T, Jinguji M, Shiga T, Kinuya S. Author Correction: A phase I clinical trial for [(131)I]meta-iodobenzylguanidine therapy in patients with refractory pheochromocytoma and paraganglioma. Scientific reports, 12:1347, 2022
10. Yagishita A, Takeda S, Katsuragawa M, Kawamura T, Matsumura H, Orita T, Umeda IO, Yabu G, Caradonna P, Takahashi T, Watanabe S, Kanayama Y, Mizuma H, Ohnuki K, Fujii H. Simultaneous visualization of multiple radionuclides in vivo. Nature biomedical engineering, 6:640-647, 2022
11. Makihara K, Yamaguchi M, Ito K, Sakaguchi K, Hori Y, Semba T, Funahashi Y, Fujii H, Terada Y. New Cluster Analysis Method for Quantitative Dynamic Contrast-Enhanced MRI Assessing Tumor Heterogeneity Induced by a Tumor-Microenvironmental Ameliorator (E7130) Treatment to a Breast Cancer Mouse Model. Journal of magnetic resonance imaging, 56:1820-1831, 2022
12. Hihara F, Matsumoto H, Yoshimoto M, Masuko T, Endo Y, Igarashi C, Tachibana T, Shinada M, Zhang MR, Kurosawa G, Sugyo A, Tsuji AB, Higashi T, Kurihara H, Ueno M, Yoshii Y. In Vitro Tumor Cell-Binding Assay to Select High-Binding Antibody and Predict Therapy Response for Personalized (64)Cu-Intraperitoneal Radioimmunotherapy against Peritoneal Dissemination of Pancreatic Cancer: A Feasibility Study. International journal of molecular sciences, 23:5807, 2022
13. Zhang X, Wakabayashi H, Kayano D, Inaki A, Kinuya S. I-131 metaiodobenzylguanidine therapy is a significant treatment option for pheochromocytoma and paraganglioma. Nuklearmedizin. Nuclear medicine, 61:231-239, 2022
14. Nakajima K, Saito S, Chen Z, Komatsu J, Maruyama K, Shirasaki N, Watanabe S, Inaki A, Ono K, Kinuya S. Diagnosis of Parkinson syndrome and Lewy-body disease using (123)I-ioflupane images and a model with image features based on machine learning. Annals of nuclear medicine, 36:765-776, 2022
15. Ohnuki K, Takenaka Y, Yoshimoto M, Fujii H. The safe handling of (211)At compounds. Annals of nuclear medicine, 36:842-843, 2022
16. Doan TKD, Umezawa M, Okubo K, Kamimura M, Yamaguchi M, Fujii H, Soga K. The effect of Gd-DOTA locations within PLGA-b-PEG micelle encapsulated IR-1061 on bimodal over-1000 nm near-infrared fluorescence and magnetic resonance imaging. Biomaterials science, 10:6244-6257, 2022
17. Fujii H, Ohnuki K, Takeda S, Katsuragawa M, Yagishita A, Yabu G, Watanabe S, Takahashi T. A Pure Tungsten Collimator Manufactured Using 3D Printing Technology for the Evaluation of 211At Radionuclide Therapy. Radioisotopes , 71:141-151, 2022
18. Ito M, Hoshino K, Takashima R, Suzuki M, Hashimoto M, Fujii H. Does case-mix classification affect predictions? A machine learning algorithm for surgical duration estimation. Health Anal, 2:100119, 2022