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Annual Report 2023

Division of Functional Imaging

Anri Inaki, Mitsuyoshi Yoshimoto, Chikayo Ide, Hirofumi Fujii, Tadayuki Takahashi, Sakiko Yasuda

Introduction

 We conduct research on nuclear medicine diagnostics, therapies, and the development of radiotheranostic agents that combine these approaches, as well as imaging technologies.

Research Activities

 We have advanced non-clinical research using the alpha-emitting radionuclides At-211 and Ac-225. In experimental cancer treatments employing antibodies labeled with At-211, we confirmed that the therapeutic efficacy of At-211-labeled antibody treatment improves by using radical scavengers to prevent antibody degradation. Additionally, we experimentally demonstrated that polyethylene filter paper, previously used in unsealed radionuclide experiments to prevent environmental contamination, is ineffective for At-211, and we raised awareness among users regarding this issue.

 In experimental cancer treatments using Ac-225-labeled peptides, we confirmed that high quality Ac-225 is required to achieve sufficient therapeutic efficacy. Meanwhile, in collaboration with industry partners, we developed a technique for producing Ac-225 with minimal isotopic contamination using electron beams from accelerators.

 To facilitate practical dose assessment for alpha radiation therapy, we also explored high-performance semiconductor gamma cameras for in vivo imaging of alpha-emitting radionuclides.

 Furthermore, we created materials that clearly explain daily life precautions for patients undergoing nuclear medicine diagnostics and therapies. To address the shortage of nuclear medicine therapy rooms for existing I-131 and Lu-177 treatments, we conducted research on efficient radionuclide containment methods.

Clinical Trials

 We planned clinical research on radiotheranostics using a CA9-targeting ligand (peptide formulation) for renal clear cell carcinoma, which is scheduled to be conducted next fiscal year.

Education

 We provided research guidance, including animal experiments, to graduate students specializing in medicine, radiological technology, and science and engineering. Additionally, we offered guidance to physicians and students from other universities.

Future Prospects

 Since nearly 100% of the radioactive isotopes used in nuclear medicine diagnostics and therapies are imported, we are advancing technical evaluations for domestic production. In parallel, we aim to develop devices that contribute to the broader adoption of nuclear medicine therapies.

List of papers published in 2023

Journal

1. Shida D, Kuchiba A, Shibata T, Hamaguchi T, Yamasaki S, Ito M, Kobatake T, Tonooka T, Masaki T, Shiozawa M, Takii Y, Uetake H, Okamura S, Ojima H, Kazama S, Takeyama H, Kanato K, Shimada Y, Murakami Y, Kanemitsu Y. Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910. Cancer science, 114:3352-3363, 2023

2. Ito Y, Hamaguchi T, Takashima A, Mizusawa J, Shimada Y, Shiozawa M, Mizoguchi N, Kodaira T, Komori K, Ohue M, Konishi K, Teraishi F, Kinouchi M, Murata K, Fujita F, Watanabe M, Iinuma G, Ishida F, Saida Y, Matsuda T, Katayama H, Fukuda H, Kanemitsu Y. Definitive S-1/mitomycin-C chemoradiotherapy for stage II/III anal canal squamous cell carcinoma: a phase I/II dose-finding and single-arm confirmatory study (JCOG0903). International journal of clinical oncology, 28:1063-1072, 2023

3. Hashimoto T, Tsukada Y, Ito M, Kanato K, Mizusawa J, Fukuda H, Tsukamoto S, Takashima A, Kanemitsu Y. Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study). BMJ open, 13:e073217, 2023

4. Hashimoto T, Maruyama S, Takii Y, Mizusawa J, Kataoka T, Fukuda H, Tsukamoto S, Takashima A, Hamaguchi T, Kanemitsu Y. A randomized phase II study comparing preoperative mFOLFOX6 versus FOLFOXIRI for locally advanced colon cancer: JCOG2006. Future oncology (London, England), 19:1897-1904, 2023

5. Hashimoto T, Tsukamoto S, Murofushi K, Ito Y, Hirano H, Tsukada Y, Sasaki K, Mizusawa J, Fukuda H, Takashima A, Kanemitsu Y. Total neoadjuvant therapy followed by a watch-and-wait strategy for patients with rectal cancer (TOWARd): protocol for single-arm phase II/III confirmatory trial (JCOG2010). BJS open, 7:zrad110, 2023

6. Imaizumi J, Shida D, Boku N, Igaki H, Itami J, Miyakita Y, Narita Y, Takashima A, Kanemitsu Y. Prognostic factors associated with the transition in treatment methods for brain metastases from colorectal cancer. International journal of clinical oncology, 28:1043-1053, 2023

7. Matsuzaki J, Kato K, Oono K, Tsuchiya N, Sudo K, Shimomura A, Tamura K, Shiino S, Kinoshita T, Daiko H, Wada T, Katai H, Ochiai H, Kanemitsu Y, Takamaru H, Abe S, Saito Y, Boku N, Kondo S, Ueno H, Okusaka T, Shimada K, Ohe Y, Asakura K, Yoshida Y, Watanabe SI, Asano N, Kawai A, Ohno M, Narita Y, Ishikawa M, Kato T, Fujimoto H, Niida S, Sakamoto H, Takizawa S, Akiba T, Okanohara D, Shiraishi K, Kohno T, Takeshita F, Nakagama H, Ota N, Ochiya T. Prediction of tissue-of-origin of early stage cancers using serum miRNomes. JNCI cancer spectrum, 7:pkac080, 2023

8. Ogata D, Tsutsui K, Namikawa K, Moritani K, Nakama K, Jinnai S, Takahashi A, Tsukamoto S, Kanemitsu Y, Yamazaki N. Treatment outcomes and prognostic factors in 47 patients with primary anorectal malignant melanoma in the immune therapy era. Journal of cancer research and clinical oncology, 149:749-755, 2023

9. Kobayashi Y, Shida D, Boku N, Yasui K, Nakamura Y, Kudose Y, Imaizumi J, Kanemitsu Y. Prognostic Factors of Bone Metastases From Colorectal Cancer in the Era of Targeted Therapy. Diseases of the colon and rectum, 66:401-409, 2023

10. Takamizawa Y, Shida D, Horie T, Tsukamoto S, Esaki M, Shimada K, Kondo T, Kanemitsu Y. Prognostic Role for Primary Tumor Location in Patients With Colorectal Liver Metastases: A Comparison of Right-Sided Colon, Left-Sided Colon, and Rectum. Diseases of the colon and rectum, 66:233-242, 2023

11. Yasui K, Shida D, Ahiko Y, Takamizawa Y, Moritani K, Tsukamoto S, Kanemitsu Y. Risk of non-colorectal cancer-related death in elderly patients with the disease: A comparison of five preoperative risk assessment indices. Cancer medicine, 12:2290-2302, 2023

12. Horie T, Kanemitsu Y, Takamizawa Y, Moritani K, Tsukamoto S, Shida D. Prognostic differences between oligometastatic and polymetastatic disease after resection in patients with colorectal cancer and hepatic or lung metastases: Retrospective analysis of a large cohort at a single institution. Surgery, 173:328-334, 2023

13. Seishima R, Okabayashi K, Ikeuchi H, Uchino M, Futami K, Noguchi T, Ohge H, Iseki Y, Watanabe K, Itabashi M, Okamoto K, Toiyama Y, Ogino T, Nakamura M, Yamada K, Wakai T, Sato Y, Kimura H, Takahashi K, Hida K, Kinugasa Y, Ishida F, Okuda J, Daito K, Koyama F, Ueno H, Yamamoto T, Yamamoto S, Hanai T, Maemoto A, Arakaki J, Komori K, Akagi Y, Shida D, Yamaguchi S, Matsuda K, Maeda K, Noake T, Nezu R, Sasaki S, Hasegawa J, Sunami E, Kanemitsu Y, Katsumata K, Uehara K, Kiyomatsu T, Suto T, Kazama S, Yamada T, Goi T, Ishihara S, Ajioka Y, Sugihara K. Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study. The American journal of gastroenterology, 118:1248-1255, 2023

14. Imaizumi J, Moritani K, Takamizawa Y, Inoue M, Tsukamoto S, Kanemitsu Y. A review of 14 cases of perianal Paget's disease: characteristics of anorectal cancer with pagetoid spread. World journal of surgical oncology, 21:17, 2023

15. Kajiwara Y, Oka S, Tanaka S, Nakamura T, Saito S, Fukunaga Y, Takamatsu M, Kawachi H, Hotta K, Ikematsu H, Kojima M, Saito Y, Yamada M, Kanemitsu Y, Sekine S, Nagata S, Yamada K, Kobayashi N, Ishihara S, Saitoh Y, Matsuda K, Togashi K, Komori K, Ishiguro M, Kuwai T, Okuyama T, Ohuchi A, Ohnuma S, Sakamoto K, Sugai T, Katsumata K, Matsushita HO, Yamano HO, Eda H, Uraoka T, Akimoto N, Kobayashi H, Ajioka Y, Sugihara K, Ueno H. Nomogram as a novel predictive tool for lymph node metastasis in T1 colorectal cancer treated with endoscopic resection: a nationwide, multicenter study. Gastrointestinal endoscopy, 97:1119-1128.e5, 2023

16. Ouchi A, Inoue M, Sato Y, Takamizawa Y, Kinoshita T, Moritani K, Komori K, Tsukamoto S, Shimizu Y, Kanemitsu Y. Lateral pelvic lymph node metastasis in T2 low rectal cancer: is TME alone sufficient for cure? Japanese journal of clinical oncology, 53:386-392, 2023

17. Fuyama K, Ogawa M, Mizusawa J, Kanemitsu Y, Fujita S, Kawahara T, Sakamaki K, Oba K. Impact of correlations between prioritized outcomes on the net benefit and its estimate by generalized pairwise comparisons. Statistics in medicine, 42:1606-1624, 2023

18. Ito T, Takayanagi D, Sekine S, Hashimoto T, Shimada Y, Matsuda M, Yamada M, Hamamoto R, Kato T, Shida D, Kanemitsu Y, Boku N, Kohno T, Takashima A, Shiraishi K. Comparison of clinicopathological and genomic profiles in anal squamous cell carcinoma between Japanese and Caucasian cohorts. Scientific reports, 13:3587, 2023

19. Nagano N, Ichihashi Y, Komatsu T, Matsuzaki H, Hata K, Watanabe T, Misawa Y, Suzuki M, Sakamoto S, Kagami Y, Kashiro A, Takeuchi K, Kanemitsu Y, Ochiai H, Watanabe R, Honda K, Urano Y. Development of fluorogenic substrates for colorectal tumor-related neuropeptidases for activity-based diagnosis. Chemical science, 14:4495-4499, 2023

20. Ueno H, Hase K, Shiomi A, Shiozawa M, Ito M, Sato T, Hashiguchi Y, Kusumi T, Kinugasa Y, Ike H, Matsuda K, Yamada K, Komori K, Takahashi K, Kanemitsu Y, Ozawa H, Ohue M, Masaki T, Takii Y, Ishibe A, Watanabe J, Toiyama Y, Sonoda H, Koda K, Akagi Y, Itabashi M, Nakamura T, Sugihara K. Optimal bowel resection margin in colon cancer surgery: prospective multicentre cohort study with lymph node and feeding artery mapping. The Lancet regional health. Western Pacific, 33:100680, 2023

21. Kataoka K, Takahashi K, Takeuchi J, Ito K, Beppu N, Ceelen W, Kanemitsu Y, Ajioka Y, Endo I, Hasegawa K, Takahashi K, Ikeda M. Correlation between recurrence-free survival and overall survival after upfront surgery for resected colorectal liver metastases. The British journal of surgery, 110:864-869, 2023

22. Kojima M, Yokota M, Yanagisawa N, Kitamura S, Amemiya K, Kawano S, Tsukada Y, Sakuyama N, Nagayasu K, Hashimoto T, Nakashima K, Jiang K, Kanemitsu Y, Fujita F, Akiba J, Notohara K, Itakura J, Sekine S, Sakashita S, Sakamoto N, Ishikawa S, Nakanishi Y, Yao T, Liang WY, Lauwers GY, Ito M, Sakamoto K, Ishii G, Ochiai A. Assessment of Elastic Laminal Invasion Contributes to an Objective pT3 Subclassification in Colon Cancer. The American journal of surgical pathology, 47:1122-1133, 2023

23. Hashimoto T, Takayanagi D, Yonemaru J, Naka T, Nagashima K, Machida E, Kohno T, Yatabe Y, Kanemitsu Y, Hamamoto R, Takashima A, Shiraishi K, Sekine S. A comprehensive appraisal of HER2 heterogeneity in HER2-amplified and HER2-low colorectal cancer. British journal of cancer, 129:1176-1183, 2023

24. Kobayashi H, Kotake K, Kawasaki M, Kanemitsu Y, Kinugasa Y, Ueno H, Maeda K, Suto T, Itabashi M, Funahashi K, Ozawa H, Koyama F, Noura S, Ishida H, Ohue M, Kiyomatsu T, Ishihara S, Koda K, Baba H, Kawada K, Hashiguchi Y, Goi T, Toiyama Y, Tomita N, Sunami E, Akagi Y, Watanabe J, Hakamada K, Nakayama G, Sugihara K, Ajioka Y. A proposed new Japanese classification of synchronous peritoneal metastases from colorectal cancer: A multi-institutional, prospective, observational study conducted by the Japanese Society for Cancer of the Colon and Rectum. Annals of gastroenterological surgery, 7:765-771, 2023

25. Tsukamoto S, Ouchi A, Komori K, Shiozawa M, Yasui M, Ohue M, Nogami H, Takii Y, Moritani K, Kanemitsu Y. A multicenter prospective observational study of lymph node metastasis patterns and short-term outcomes of extended lymphadenectomy in right-sided colon cancer. Annals of gastroenterological surgery, 7:940-948, 2023

26. Terasaki M, Tsuruoka K, Tanaka T, Maeda H, Shibata M, Miyashita K, Kanemitsu Y, Sekine S, Takahashi M, Yagishita S, Hamada A. Fucoxanthin Inhibits Development of Sigmoid Colorectal Cancer in a PDX Model With Alterations of Growth, Adhesion, and Cell Cycle Signals. Cancer genomics & proteomics, 20:686-705, 2023