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Target Alpha Therapy with Thorium-227.

Abstract

Targeted alpha therapy (TAT) can deliver high localized burden of radiation selectively to cancer cells as well as the tumor microenvironment, while minimizing toxicity to normal surrounding cell. Radium-223 (223Ra), the first-in-class a-emitter approved for bone metastatic castration-resistant prostate cancer has shown the ability to prolong patient survival. Targeted Thorium-227 (227Th) conjugates represent a new class of therapeutic radiopharmaceuticals for TAT. They are comprised of the α-emitter 227Th complexed to a chelator conjugated to a tumor-targeting monoclonal antibody. In this review, the authors will focus out interest on this therapeutic agent. In recent studies 227Th-labeled radioimmunoconjugates showed a relevant stability both in serum and vivo conditions with a significant antigen-dependent inhibition of cell growth. Unlike 223Ra, the parent radionuclide 227Th can form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. The authors discuss the future potential role of 227Th TAT in the treatment of several solid as well as hematologic malignancies.

Authors+Show Affiliations

Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.Department of Oncology and Hemato-oncology, University of Milan "Statale," Milan, Italy.Unit of Nuclear Medicine, Department of Medicine, Surgical and Experimental Science, University of Sassari, Sassari, Italy.Unit of Nuclear Medicine, Department of Medicine, Surgical and Experimental Science, University of Sassari, Sassari, Italy.Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31967907

Citation

Frantellizzi, Viviana, et al. "Target Alpha Therapy With Thorium-227." Cancer Biotherapy & Radiopharmaceuticals, 2020.
Frantellizzi V, Cosma L, Brunotti G, et al. Target Alpha Therapy with Thorium-227. Cancer Biother Radiopharm. 2020.
Frantellizzi, V., Cosma, L., Brunotti, G., Pani, A., Spanu, A., Nuvoli, S., ... De Vincentis, G. (2020). Target Alpha Therapy with Thorium-227. Cancer Biotherapy & Radiopharmaceuticals, doi:10.1089/cbr.2019.3105.
Frantellizzi V, et al. Target Alpha Therapy With Thorium-227. Cancer Biother Radiopharm. 2020 Jan 20; PubMed PMID: 31967907.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Target Alpha Therapy with Thorium-227. AU - Frantellizzi,Viviana, AU - Cosma,Laura, AU - Brunotti,Gabriele, AU - Pani,Arianna, AU - Spanu,Angela, AU - Nuvoli,Susanna, AU - De Cristofaro,Flaminia, AU - Civitelli,Liana, AU - De Vincentis,Giuseppe, Y1 - 2020/01/20/ PY - 2020/1/23/entrez PY - 2020/1/23/pubmed PY - 2020/1/23/medline KW - cancer KW - radionuclide therapy KW - review KW - targeted therapy KW - thorium-227 KW - α-emitter JF - Cancer biotherapy & radiopharmaceuticals JO - Cancer Biother. Radiopharm. N2 - Targeted alpha therapy (TAT) can deliver high localized burden of radiation selectively to cancer cells as well as the tumor microenvironment, while minimizing toxicity to normal surrounding cell. Radium-223 (223Ra), the first-in-class a-emitter approved for bone metastatic castration-resistant prostate cancer has shown the ability to prolong patient survival. Targeted Thorium-227 (227Th) conjugates represent a new class of therapeutic radiopharmaceuticals for TAT. They are comprised of the α-emitter 227Th complexed to a chelator conjugated to a tumor-targeting monoclonal antibody. In this review, the authors will focus out interest on this therapeutic agent. In recent studies 227Th-labeled radioimmunoconjugates showed a relevant stability both in serum and vivo conditions with a significant antigen-dependent inhibition of cell growth. Unlike 223Ra, the parent radionuclide 227Th can form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. The authors discuss the future potential role of 227Th TAT in the treatment of several solid as well as hematologic malignancies. SN - 1557-8852 UR - https://www.unboundmedicine.com/medline/citation/31967907/Target_Alpha_Therapy_with_Thorium-227 L2 - https://www.liebertpub.com/doi/full/10.1089/cbr.2019.3105?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -