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  1. Article ; Online: Synthesis and evaluation of novel trifunctional chelating agents for pretargeting approach using albumin binder to improve tumor accumulation.

    Tsuchihashi, Shohei / Nakashima, Kazuma / Watanabe, Hiroyuki / Ono, Masahiro

    Nuclear medicine and biology

    2024  Volume 132-133, Page(s) 108911

    Abstract: Introduction: The pretargeting approach consists of in vivo ligation between pre-injected antibodies and low-molecular-weight radiolabeled effectors. The advantage of the pretargeting approach is to improve a tumor-to-background ratio, but the ... ...

    Abstract Introduction: The pretargeting approach consists of in vivo ligation between pre-injected antibodies and low-molecular-weight radiolabeled effectors. The advantage of the pretargeting approach is to improve a tumor-to-background ratio, but the disadvantage is to compromise tumor accumulation. In this study, we applied albumin binder (ALB) to the pretargeting approach to overcome low tumor accumulation.
    Methods: We synthesized two novel trifunctional effectors containing an ALB moiety, a chelator, and a different tetrazine and two corresponding effectors without an ALB moiety. Albumin-binding assays and stability assays were performed using
    Results: In albumin-binding assays, ALB-containing effectors exhibited a marked binding to albumin. Two ALB-containing effectors showed the difference in the reactivity and the slight difference in the stability. In biodistribution studies without the pretargeting approach, two ALB-containing effectors showed different pharmacokinetics in blood retention. With the pretargeting approach, the tumor accumulation was improved by the introduction of ALB and the highest tumor accumulation was observed in using the ALB-containing effector with higher blood retention.
    Conclusion: These results suggest that the application of ALB to the pretargeting approach is effective to improve tumor accumulation, and the structure of tetrazine influences the utility of ALB-containing effectors.
    Language English
    Publishing date 2024-04-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1138098-6
    ISSN 1872-9614 ; 0883-2897 ; 0969-8051
    ISSN (online) 1872-9614
    ISSN 0883-2897 ; 0969-8051
    DOI 10.1016/j.nucmedbio.2024.108911
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Development of Novel Trifunctional Chelating Agents That Enhance Tumor Retention of Radioimmunoconjugates.

    Nakashima, Kazuma / Watanabe, Hiroyuki / Ono, Masahiro

    Journal of medicinal chemistry

    2023  Volume 66, Issue 18, Page(s) 12812–12827

    Abstract: Chelator-containing radioimmunoconjugates (RICs) composed of monoclonal antibodies, chelators, and radiometals exhibit broad potential for cancer diagnosis or therapy. In this study, we developed novel trifunctional chelating agents that enhance the ... ...

    Abstract Chelator-containing radioimmunoconjugates (RICs) composed of monoclonal antibodies, chelators, and radiometals exhibit broad potential for cancer diagnosis or therapy. In this study, we developed novel trifunctional chelating agents that enhance the tumor retention of RICs, MDPEI2, and MDPEI4, which contain the metal chelator DOTA, a maleimide moiety, and diethylenetriamine (PEI2) or tetraethylenepentamine (PEI4), respectively, as a poly(ethylenimine) (PEI) scaffold for the addition of positive charges to the radiometabolites of RICs to reduce their release from tumor cells. Trastuzumab radiolabeled by [
    MeSH term(s) Humans ; Chelating Agents ; Immunoconjugates ; Antibodies, Monoclonal ; Neoplasms/diagnostic imaging ; Neoplasms/drug therapy ; Trastuzumab ; Cell Line, Tumor
    Chemical Substances Chelating Agents ; Immunoconjugates ; Antibodies, Monoclonal ; Trastuzumab (P188ANX8CK)
    Language English
    Publishing date 2023-09-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c00472
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Application of the Chelator-Based Clickable Radiotheranostic Platform to Moderate-Molecular-Weight Ligands.

    Nakashima, Kazuma / Iikuni, Shimpei / Watanabe, Hiroyuki / Ono, Masahiro

    ACS medicinal chemistry letters

    2022  Volume 13, Issue 10, Page(s) 1642–1647

    Abstract: We have reported that the chelator-based clickable radiotheranostic platform, ADIBO-DOTADG-ALB (ADA), has favorable properties as a radiotheranostic platform for low-molecular-weight ligands. In this study, we evaluated the applicability of ADA to ... ...

    Abstract We have reported that the chelator-based clickable radiotheranostic platform, ADIBO-DOTADG-ALB (ADA), has favorable properties as a radiotheranostic platform for low-molecular-weight ligands. In this study, we evaluated the applicability of ADA to moderate-molecular-weight ligands to expand the utility of the ADA platform. As a moderate-molecular-weight ligand, we selected exendin-4, a peptide-based agonist to glucagon-like peptide-1 receptor (GLP-1R). An exendin-4-incorporated ADA derivative, exendin-4-Cys
    Language English
    Publishing date 2022-09-02
    Publishing country United States
    Document type Journal Article
    ISSN 1948-5875
    ISSN 1948-5875
    DOI 10.1021/acsmedchemlett.2c00320
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Development of a novel radiotheranostic platform with a DOTA-based trifunctional chelating agent.

    Nakashima, Kazuma / Iikuni, Shimpei / Watanabe, Hiroyuki / Ono, Masahiro

    Chemical communications (Cambridge, England)

    2021  Volume 57, Issue 52, Page(s) 6432–6435

    Abstract: Radiotheranostics has attracted attention as a powerful strategy for treating cancer patients with precision medicine. We designed and synthesized a novel DOTA-based trifunctional agent, ADIBO-DOTADG-ALB (ADA), which allowed compounds with targeting ... ...

    Abstract Radiotheranostics has attracted attention as a powerful strategy for treating cancer patients with precision medicine. We designed and synthesized a novel DOTA-based trifunctional agent, ADIBO-DOTADG-ALB (ADA), which allowed compounds with targeting ligands, radiometals, and an albumin binder to be readily prepared. ADA exhibited promising properties as a theranostic platform.
    Language English
    Publishing date 2021-05-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 1472881-3
    ISSN 1364-548X ; 1359-7345 ; 0009-241X
    ISSN (online) 1364-548X
    ISSN 1359-7345 ; 0009-241X
    DOI 10.1039/d1cc00823d
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Development of Novel

    Tsuchihashi, Shohei / Nakashima, Kazuma / Tarumizu, Yuta / Ichikawa, Hiroaki / Jinda, Hiroki / Watanabe, Hiroyuki / Ono, Masahiro

    Journal of medicinal chemistry

    2023  Volume 66, Issue 12, Page(s) 8043–8053

    Abstract: Prostate-specific membrane antigen (PSMA) is a promising target for metastatic castration-resistant prostate cancer. We previously reported the effectiveness of PSMA-DA1 as a PSMA-targeting radiotheranostic agent containing an albumin binder moiety. To ... ...

    Abstract Prostate-specific membrane antigen (PSMA) is a promising target for metastatic castration-resistant prostate cancer. We previously reported the effectiveness of PSMA-DA1 as a PSMA-targeting radiotheranostic agent containing an albumin binder moiety. To further enhance tumor uptake, we newly designed PSMA-NAT-DA1 (PNT-DA1) by the introduction of a lipophilic linker into PSMA-DA1. The PSMA affinity of [
    MeSH term(s) Humans ; Male ; Albumins ; Antigens, Surface ; Cell Line, Tumor ; Glutamate Carboxypeptidase II ; Indium/chemistry ; Prostatic Neoplasms/pathology ; Radiopharmaceuticals/therapeutic use ; Single Photon Emission Computed Tomography Computed Tomography ; Indium Radioisotopes/chemistry ; Indium Radioisotopes/therapeutic use
    Chemical Substances Albumins ; Antigens, Surface ; Glutamate Carboxypeptidase II (EC 3.4.17.21) ; Indium (045A6V3VFX) ; Radiopharmaceuticals ; Indium Radioisotopes
    Language English
    Publishing date 2023-06-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c00346
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Development of a novel radiotheranostic platform with a DOTA-based trifunctional chelating agent

    Nakashima, Kazuma / Iikuni, Shimpei / Watanabe, Hiroyuki / Ono, Masahiro

    Chemical communications. 2021 June 29, v. 57, no. 52

    2021  

    Abstract: Radiotheranostics has attracted attention as a powerful strategy for treating cancer patients with precision medicine. We designed and synthesized a novel DOTA-based trifunctional agent, ADIBO-DOTADG-ALB (ADA), which allowed compounds with targeting ... ...

    Abstract Radiotheranostics has attracted attention as a powerful strategy for treating cancer patients with precision medicine. We designed and synthesized a novel DOTA-based trifunctional agent, ADIBO-DOTADG-ALB (ADA), which allowed compounds with targeting ligands, radiometals, and an albumin binder to be readily prepared. ADA exhibited promising properties as a theranostic platform.
    Keywords albumins ; ligands ; precision medicine
    Language English
    Dates of publication 2021-0629
    Size p. 6432-6435.
    Publishing place The Royal Society of Chemistry
    Document type Article
    ZDB-ID 1472881-3
    ISSN 1364-548X ; 1359-7345 ; 0009-241X
    ISSN (online) 1364-548X
    ISSN 1359-7345 ; 0009-241X
    DOI 10.1039/d1cc00823d
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Radiotheranostics Using a Novel

    Iikuni, Shimpei / Tarumizu, Yuta / Nakashima, Kazuma / Higaki, Yusuke / Ichikawa, Hiroaki / Watanabe, Hiroyuki / Ono, Masahiro

    Journal of medicinal chemistry

    2021  Volume 64, Issue 18, Page(s) 13429–13438

    Abstract: ... ...

    Abstract 225
    MeSH term(s) Actinium/chemistry ; Animals ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/metabolism ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Cyclams/chemical synthesis ; Cyclams/metabolism ; Cyclams/pharmacokinetics ; Cyclams/therapeutic use ; Glutamate Carboxypeptidase II/metabolism ; Humans ; Ligands ; Male ; Membrane Glycoproteins/metabolism ; Mice, Inbred ICR ; Mice, SCID ; Precision Medicine/methods ; Prostatic Neoplasms, Castration-Resistant/diagnostic imaging ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/metabolism ; Radiopharmaceuticals/chemical synthesis ; Radiopharmaceuticals/metabolism ; Radiopharmaceuticals/pharmacokinetics ; Radiopharmaceuticals/therapeutic use ; Single Photon Emission Computed Tomography Computed Tomography ; Urea/analogs & derivatives ; Urea/metabolism ; Urea/pharmacokinetics ; Urea/therapeutic use ; Xenograft Model Antitumor Assays ; Mice
    Chemical Substances Actinium-225 ; Antineoplastic Agents ; Cyclams ; Ligands ; Membrane Glycoproteins ; Radiopharmaceuticals ; Urea (8W8T17847W) ; Glutamate Carboxypeptidase II (EC 3.4.17.21) ; PSMA protein, mouse (EC 3.4.17.21) ; Actinium (NIK1K0956U)
    Language English
    Publishing date 2021-09-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.1c00772
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Synthesis and evaluation of

    Nakashima, Kazuma / Iikuni, Shimpei / Okada, Yuya / Watanabe, Hiroyuki / Shimizu, Yoichi / Nakamoto, Yuji / Ono, Masahiro

    Nuclear medicine and biology

    2020  Volume 93, Page(s) 46–53

    Abstract: Introduction: Carbonic anhydrase-IX (CA-IX) is markedly overexpressed in many types of solid tumors promoting tumorigenicity and tumor growth. We synthesized novel : Methods: [: Results: To evaluate their fundamental properties, [: Conclusion: ... ...

    Abstract Introduction: Carbonic anhydrase-IX (CA-IX) is markedly overexpressed in many types of solid tumors promoting tumorigenicity and tumor growth. We synthesized novel
    Methods: [
    Results: To evaluate their fundamental properties, [
    Conclusion: These results indicate that
    MeSH term(s) Animals ; Carbonic Anhydrase IX/metabolism ; Chemistry Techniques, Synthetic ; Gallium Radioisotopes/chemistry ; HT29 Cells ; Humans ; Mice ; Positron-Emission Tomography/methods ; Thiadiazoles/chemical synthesis ; Thiadiazoles/chemistry
    Chemical Substances Gallium Radioisotopes ; Thiadiazoles ; Gallium-68 (98B30EPP5S) ; Carbonic Anhydrase IX (EC 4.2.1.1)
    Language English
    Publishing date 2020-11-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1138098-6
    ISSN 1872-9614 ; 0883-2897 ; 0969-8051
    ISSN (online) 1872-9614
    ISSN 0883-2897 ; 0969-8051
    DOI 10.1016/j.nucmedbio.2020.11.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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