The DOI matches its Crossref record; 134 of the 141 references it cites were found in a registry or an index.
Bismuth-213 for targeted radionuclide therapy: from atom to bedside.
Open accessPublished version of a preprint
Abstract
Besides external high-energy photon or proton beam therapy, targeted radionuclide therapy (TRNT) is an alternative approach to deliver radiation to cancer cells. TRNT is distributed within the body by the vascular system and allows targeted irradiation of a primary tumor and all its metastases, resulting in substantially less collateral damage to normal tissues as compared to ex-ternal beam radiotherapy (EBRT). It is a systemic cancer therapy, tackling systemic spread of the disease, which is the cause of death in most cancer patients. The α-emitting radionuclide bis-muth-213 (213Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with 213Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of 225Ac and its daughter 213Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth, and general considerations for designing a 213Bi-radiopharmaceutical are provided. Finally, we will provide an overview of preclinical and clinical studies involving 213Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.
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“It is important to mention that the availability of appropriate cyclotrons worldwide [energy range 15–25 MeV (101)] makes the production of 225Ac feasible for basic and applied research (94).”
From Alpha-peptide receptor radionuclide therapy using actinium-225 labeled somatostatin receptor agonists and antagonists (2022) · cites this paper as [94]
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Cites
Phase 3 Trial of 177 Lu-Dotatate for Midgut Neuroendocrine Tumors
Strosberg, J., El-Haddad, G., Wolin, E., Hendifar, A., Yao, J., Chasen, B., Mittra, E., Kunz, P. L., Kulke, M. H., Jacene, H., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1607427 · Cited by 3,308
Relativistic effects in structural chemistry
Pyykkö, P. (1988) · Chemical Reviews · doi:10.1021/cr00085a006 · Cited by 3,077 · cited 1×
“, core-like nature of the 6s electrons), the term “inert pair effect” [36], or “nonhybridization effect” has often been used [37].”
MethodHard and soft acids and bases, HSAB, part 1: Fundamental principles
Pearson, R. G. (1968) · Journal of Chemical Education · doi:10.1021/ed045p581 · Cited by 2,566
Engineered antibody fragments and the rise of single domains
Holliger, P., & Hudson, P. J. (2005) · Nature Biotechnology · doi:10.1038/nbt1142 · Cited by 1,928 · cited 1×
“2 Antibody fragments Recent advances in bioengineering have led to the the development of antibody fragments such as Fab (50 kDa), F(ab’)2 (110kDa), 25-kDa single-chain Fv (scFv), diabodies (55 kDa), nanobodies (15kDa) and minibodies (80 kDa) without affecting their affinity and specificity [94].”
BackgroundMatching chelators to radiometals for radiopharmaceuticals
Price, E. W., & Orvig, C. (2013) · Chemical Society Reviews · doi:10.1039/c3cs60304k · Cited by 1,064 · cited 6×
“The presence of the cyclohexyl moiety of CHX-A”-DTPA provides the chelator with additional rigidity and imposes a significant degree of preorganization on the metal ion binding site, augmenting kinetic inertness, but impeding radiolabeling kinetics as compared with DTPA [3].”
BackgroundMethodInfluentialLindner, T., Loktev, A., Altmann, A., Giesel, F. L., Kratochwil, C., Debus, J., Jäger, D., Mier, W., & Haberkorn, U. (2018) · Journal of Nuclear Medicine · doi:10.2967/jnumed.118.210443 · Cited by 961
Guo, Z., & Sadler, P. J. (1999) · Angewandte Chemie International Edition · doi:10.1002/(sici)1521-3773(19990601)38:11 · Cited by 840
A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts
Loktev, A., Lindner, T., Mier, W., Debus, J., Altmann, A., Jäger, D., Giesel, F. L., Kratochwil, C., Barthe, P., Roumestand, C., et al. (2018) · Journal of Nuclear Medicine · doi:10.2967/jnumed.118.210435 · Cited by 784
Giesel, F. L., Kratochwil, C., Lindner, T., Marschalek, M. M., Loktev, A., Lehnert, W., Debus, J., Jäger, D., Flechsig, P., Altmann, A., et al. (2018) · Journal of Nuclear Medicine · doi:10.2967/jnumed.118.215913 · Cited by 748
Bismuth Compounds and Preparations with Biological or Medicinal Relevance
Briand, G. G., & Burford, N. (1999) · Chemical Reviews · doi:10.1021/cr980425s · Cited by 599 · cited 1×
“However, Bi compounds are or were used in a wide spectrum of applications ranging from non-toxic pigments and catalysts to biocompatible additives in dental materials and remedies in human and veterinary medicine [34,35].”
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Research works printed but not linked: 1
- Finn, 2017, A Phase 2 Study of Actinium-225 (225Ac)-Lintuzumab in Older Patients with Previously Untreated Acute Myeloid Leukemia (AML) Unfit for Intensive Chemotherapy, Blood, 130, 2638
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Sorted by citations
Items 101–119 of 119
Medical Physics in Practice: Tools, Techniques, and Case Studies
Rashid, L. A. K., Sadiq, F. S. W., miran, K. A. B., Jabbar, M. A. Y., Mahdi, M. J. S., & Dhaif, Z. J. Y. (2025) · Bright Sky Publications eBooks · doi:10.62906/bs.book.352
Koniar, H., & Schaffer, P. C. (2025) · Royal Society of Chemistry eBooks · doi:10.1039/9781837677139-00056
van der Heide, C. D., Ma, H., Hoorens, M. W. H., Campeiro, J. D., Stuurman, D. C., de Ridder, C. M. A., Seimbille, Y., & Dalm, S. U. (2024) · Figshare · doi:10.6084/m9.figshare.26401912
Chelator-Free Radiometal Labeling Inside Engineered AffibodiesPreprint
Davies, L. J., Bruchertseifer, F., Morgenstern, A., Spreckelmeyer, S., & Nitsche, C. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.28.702152
Voss, S., Sagar, A., Tiberghien, A. C., Hughes, R. J. L., Chen, L., Rioja, I., Frigerio, M., Skynner, M. J., & Spring, D. R. (2026) · Journal of Peptide Science · doi:10.1002/psc.70071
“Bismuth-213, a radioactive isotope with a half-life of ~46 min, decays through two different pathways to bismuth-209, emitting either way an alpha particle in the process [98, 99].”
Hedefe Yönelik Alfa Tedavisi Fiziksel Prensiplerden Klinik Uygulamaya
Beytur, F. (2026) · Akademisyen Kitabevi eBooks · doi:10.37609/akya.4060
Radioimmunotheranostics for cancer imaging and therapy
Reilly, R. M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-29808-0.00091-1
Xu, L. L., Singh, S. K., Gaspar, N., Fan, J., Viglianti, B. L., & Zinn, K. R. (2026) · Molecules · doi:10.3390/molecules31061019
“…to the direct dsDNA damage, alpha-particles generate reactive oxygen species when they interact with water to a higher degree than other radiation types, resulting in damage to proteins and phospholipids associated with the cell membrane, mitochondria, endoplasmic reticulum, and lysosomes [69–71].”
Bonneux, C., Pérez, S. R., Heinitz, S., Bogaerts, V., de Voorde, M. V., Cardinaels, T., Ooms, M., Dehaen, W., & Opsomer, T. (2026) · EJNMMI Radiopharmacy and Chemistry · doi:10.1186/s41181-026-00438-y
“In contrast, DOTA did not reach quantitative conversion, as elevated temperatures are typically required for this chelator (Cassells et al. 2021).”
Chelator‐Free Radiometal Labeling Inside Engineered Affibodies
Davies, L. J., Somathilake, U., Kumaresan, S., Bruchertseifer, F., Morgenstern, A., Spreckelmeyer, S., & Nitsche, C. (2026) · Angewandte Chemie International Edition · doi:10.1002/anie.6657079
“For the first time, we also explore the loading and stability of the radioactive isotope 213 Bi, an α -emitter used in TAT [25].”
Chelator‐Free Radiometal Labeling Inside Engineered Affibodies
Davies, L. J., Somathilake, U., Kumaresan, S., Bruchertseifer, F., Morgenstern, A., Spreckelmeyer, S., & Nitsche, C. (2026) · Angewandte Chemie · doi:10.1002/ange.6657079
Asti, M., Tosato, M., Franchi, S., & Marco, V. D. (2026) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2026.218062
Ige, O. O., Longmena, T. S., & Jonah, S. A. (2026) · Nuclear Energy and Technology · doi:10.3897/nucet.12.178562
Design Strategies for Developing Chiral Macrocyclic Chelators as a Diagnostic Tool
Zhu, Y., & Law, G. (2026) · Accounts of Chemical Research · doi:10.1021/acs.accounts.6c00081
Erder, E., Singh, S. K., Xu, L. L., Nayback, C., Fan, J., Grimm, T., Isaac, D., Zamiara, M., & Zinn, K. R. (2026) · EJNMMI Research · doi:10.1186/s13550-026-01528-3
Spahn, M. A., Loy, T. V., Deroose, C. M., Celen, S., Schols, D., Bormans, G. M., Kleynhans, J., & Cleeren, F. (2026) · Pharmaceuticals · doi:10.3390/ph19081160
“In our earlier study, we demonstrated that [ 18 F]AlF-NOTA-SC possesses highly favorable pharmacokinetic characteristics, including strong tumor uptake, low off-target accumulation, and superior imaging performance compared with [ 18 F]FDG.”
InfluentialОрлова, М. А., Spiridonov, V. V., Трофимова, Т. П., Evdokimov, A. A., Орлов, А. П., Borodkov, A. S., Замуруева, Л. С., Yaroslavov, A. A., & Kalmykov, S. N. (2026) · Journal of Radioanalytical and Nuclear Chemistry · doi:10.1007/s10967-026-11094-6
Piacenza, P., Tei, L., Milanesio, M., & Lopresti, M. (2026) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2026.147872
Metadata
- Authors
- Ahenkorah, S., Cassells, I., Deroose, C. M., Cardinaels, T., Burgoyne, A. R., Bormans, G., Ooms, M., & Cleeren, F.
- Affiliations
- Belgian Nuclear Research Centre (BE)
- Universitair Ziekenhuis Leuven (BE)
- KU Leuven (BE)
- Corresponding author
- Ooms, Maarten
- Cleeren, Frederik
- ORCID
- Venue
- Pharmaceutics
- Publisher
- MDPI AG
- Published
- 2021-04-21
- Volume
- 13
- Issue
- 5
- Pages
- 599
- ISSN
- 1999-4923 (ISSN-L)
- PMC
- PMC8143329
- OpenAlex
- W3145208530
- Cited by
- 120
- References
- 141
- Citations by year
- 2026: 21 · 2025: 26 · 2024: 24 · 2023: 24 · 2022: 19 · 2021: 6
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Pharmaceutics (publishedVersion, cc-by)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fonds Wetenschappelijk Onderzoek (12R3119N)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Physical Sciences › Physics and Astronomy › Radiation › Radioactivity and Radon Measurements
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Chemical Reactions and Isotopes
- Keywords
- bismuth-213, targeted radionuclide therapy, targeted alpha therapy, actinium-225, radioisotope production, bifunctional chelators, macrocyclic chelators, radiopharmaceutical design, bismuth chemistry, alpha-emitting radionuclides, cancer therapy
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