The Actinium Aqua Ion: A Century in the Making

“…[1][2][3] However, recent discoveries tend to support its reassignment as an actual fblock element. [4][5][6][7] All isotopes of actinium are unstable and highly radioactive. Specifically, the Ac isotope 225 Ac, as a promising anticancer therapeutic agent, makes targeted radionuclide therapy a powerful cancer treatment strategy.…”

Section: Introductionmentioning

confidence: 99%

Stabilization of hydrated Ac^III cation: the role of superatom states in actinium-water bonding

Grover

Schreckenbach

2021

Chem. Sci.

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“…Analysis of the [ 227 Ac]Ac III -aqua ion by EXAFS spectroscopy suggests that the inner coordination sphere contains 10.9 ± 0.5 water molecules with an average bond distance of 2.63(1) Å. The [ 227 Ac]Ac III -aqua ion coordination number is slightly higher than other actinide and lanthanide aqua ions and is the only example of an 11-coordinate aqua complex. , …”

Section: The Rise Of Targeted α Particle Therapymentioning

confidence: 97%

“…The [ 227 Ac]Ac IIIaqua ion coordination number is slightly higher than other actinide and lanthanide aqua ions and is the only example of an 11-coordinate aqua complex. 198,200 The potential of using actinium-225 for radioimmunotherapy was realized in seminal preclinical work developing antibody conjugates using actinium-225. 201−204 This initial work used DOTA as a chelator for actinium-225, but radiolabeling with DOTA requires heating to relatively high temperatures that often denature antibodies.…”

Section: Radionuclide Therapy With Actinium-225mentioning

confidence: 99%

Theranostic Nuclear Medicine with Gallium-68, Lutetium-177, Copper-64/67, Actinium-225, and Lead-212/203 Radionuclides

Morgan,

Rudd,

Noor

et al. 2023

Chem. Rev.

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Molecular changes in malignant tissue can lead to an increase in the expression levels of various proteins or receptors that can be used to target the disease. In oncology, diagnostic imaging and radiotherapy of tumors is possible by attaching an appropriate radionuclide to molecules that selectively bind to these target proteins. The term “theranostics” describes the use of a diagnostic tool to predict the efficacy of a therapeutic option. Molecules radiolabeled with γ-emitting or β+-emitting radionuclides can be used for diagnostic imaging using single photon emission computed tomography or positron emission tomography. Radionuclide therapy of disease sites is possible with either α-, β-, or Auger-emitting radionuclides that induce irreversible damage to DNA. This Focus Review centers on the chemistry of theranostic approaches using metal radionuclides for imaging and therapy. The use of tracers that contain β+-emitting gallium-68 and β-emitting lutetium-177 will be discussed in the context of agents in clinical use for the diagnostic imaging and therapy of neuroendocrine tumors and prostate cancer. A particular emphasis is then placed on the chemistry involved in the development of theranostic approaches that use copper-64 for imaging and copper-67 for therapy with functionalized sarcophagine cage amine ligands. Targeted therapy with radionuclides that emit α particles has potential to be of particular use in late-stage disease where there are limited options, and the role of actinium-225 and lead-212 in this area is also discussed. Finally, we highlight the challenges that impede further adoption of radiotheranostic concepts while highlighting exciting opportunities and prospects.

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“…For example, SPECT isotope indium-111 ( 111 In, t 1/2 = 2.8 d, EC (100%), I γ 94.1% (245.4 keV), 90.6% (171.3 keV)) and PET isotope zirconium-89 ( 89 Zr, t 1/2 = 78.4 h, β + (23%)) are popular isotopes for nuclear imaging of radiopharmaceuticals with long biological half-lives, such as monoclonal antibodies (mAbs). Therapeutic radiometals, on the other hand, emit cytotoxic radiation in the form of alpha (α) particles, beta (β − ) particles, or Meitner-Auger electrons (MAEs) and within the last five years, actinium-225 ( 225 Ac, t 1/2 9.9 d), a radiometal with four net α and two β − decays, has emerged as a popular isotope for targeted alpha therapy (TAT) (Thierer and Tomson 2017 ; Morgenstern et al 2018 ). Although in its early stages, promising 225 Ac-labeled drug candidates have been generated, with some in clinical trials (Morgenstern et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Development of a multi faceted platform containing a tetrazine, fluorophore and chelator: synthesis, characterization, radiolabeling, and immuno-SPECT imaging

McDonagh

McNeil

Rousseau³

et al. 2022

EJNMMI radiopharm. chem.

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Background Combining optical (fluorescence) imaging with nuclear imaging has the potential to offer a powerful tool in personal health care, where nuclear imaging offers in vivo functional whole-body visualization, and the fluorescence modality may be used for image-guided tumor resection. Varying chemical strategies have been exploited to fuse both modalities into one molecular entity. When radiometals are employed in nuclear imaging, a chelator is typically inserted into the molecule to facilitate radiolabeling; the availability of the chelator further expands the potential use of these platforms for targeted radionuclide therapy if a therapeutic radiometal is employed. Herein, a novel mixed modality scaffold which contains a tetrazine (Tz)––for biomolecule conjugation, fluorophore—for optical imaging, and chelator—for radiometal incorporation, in one construct is presented. The novel platform was characterized for its fluorescence properties, radiolabeled with single-photon emission computed tomography (SPECT) isotope indium-111 (111In3+) and therapeutic alpha emitter actinium-225 (225Ac3+). Both radiolabels were conjugated in vitro to trans-cyclooctene (TCO)-modified trastuzumab; biodistribution and immuno-SPECT imaging of the former conjugate was assessed. Results Key to the success of the platform synthesis was incorporation of a 4,4′-dicyano-BODIPY fluorophore. The route gives access to an advanced intermediate where final chelator-incorporated compounds can be easily accessed in one step prior to radiolabeling or biomolecule conjugation. The DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) conjugate was prepared, displayed good fluorescence properties, and was successfully radiolabeled with 111In & 225Ac in high radiochemical yield. Both complexes were then separately conjugated in vitro to TCO modified trastuzumab through an inverse electron demand Diels–Alder (IEDDA) reaction with the Tz. Pilot small animal in vivo immuno-SPECT imaging with [111In]In-DO3A-BODIPY-Tz-TCO-trastuzumab was also conducted and exhibited high tumor uptake (21.2 ± 5.6%ID/g 6 days post-injection) with low uptake in non-target tissues. Conclusions The novel platform shows promise as a multi-modal probe for theranostic applications. In particular, access to an advanced synthetic intermediate where tailored chelators can be incorporated in the last step of synthesis expands the potential use of the scaffold to other radiometals. Future studies including validation of ex vivo fluorescence imaging and exploiting the pre-targeting approach available through the IEDDA reaction are warranted.

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The Actinium Aqua Ion: A Century in the Making

Cited by 4 publications

References 9 publications

Stabilization of hydrated Ac^III cation: the role of superatom states in actinium-water bonding

Stabilization of hydrated Ac^III cation: the role of superatom states in actinium-water bonding

Theranostic Nuclear Medicine with Gallium-68, Lutetium-177, Copper-64/67, Actinium-225, and Lead-212/203 Radionuclides

Development of a multi faceted platform containing a tetrazine, fluorophore and chelator: synthesis, characterization, radiolabeling, and immuno-SPECT imaging

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The Actinium Aqua Ion: A Century in the Making

Cited by 4 publications

References 9 publications

Stabilization of hydrated AcIII cation: the role of superatom states in actinium-water bonding

Stabilization of hydrated AcIII cation: the role of superatom states in actinium-water bonding

Theranostic Nuclear Medicine with Gallium-68, Lutetium-177, Copper-64/67, Actinium-225, and Lead-212/203 Radionuclides

Development of a multi faceted platform containing a tetrazine, fluorophore and chelator: synthesis, characterization, radiolabeling, and immuno-SPECT imaging

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Product

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Stabilization of hydrated Ac^III cation: the role of superatom states in actinium-water bonding

Stabilization of hydrated Ac^III cation: the role of superatom states in actinium-water bonding