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Advanced Systems in Targeted Alpha Particle Therapy
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Advanced Systems in Targeted Alpha Particle Therapy

A special issue of Materials (ISSN 1996-1944). This special issue belongs to the section "Advanced Nanomaterials and Nanotechnology".

Deadline for manuscript submissions: closed (10 August 2022) | Viewed by 9902

Special Issue Editor

Prof. Ján Kozempel

E-Mail Website
Guest Editor
Department of Nuclear Chemistry, Czech Technical University in Prague, Prague, Czech Republic
Interests: radiochemistry; radiopharmacy; nanotechnology; radionuclide production

Special Issue Information

Dear Colleagues,

It has now been almost 30 years of research and development efforts in the rediscovered field of targeted alpha particle therapy. Many novel isotope production methods, new targeting molecules, and nanocarriers together with preclinical or clinical trials and first-in-patient studies have moved this field forward by leaps and bounds. This successful progress has resulted in the global acceptance of alpha emitters, like the 223RaCl2 or 225Ac-PSMA-617, powerful tools in clinical praxis, and experimental cancer treatment. Targeted alpha particle therapy (TAT) has become a regular therapeutic modality in the treatment of cancer.

This Special Issue focuses on the latest innovations and studies in the field of TAT, including the preparation and testing of novel carriers, targeting systems, and medical devices, particularly those exploiting or suppressing the nuclear recoil effect in so-called in vivo radionuclide generators. In vitro stability and in vivo biodistribution studies, dosimetric studies, therapeutic efficacy determinations in various models, clinical trials, and other related research are welcome as full papers, communications, or reviews.

Prof. Ján Kozempel
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Materials is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Alpha particle
  • Chain decay
  • In vivo generators
  • Nuclear recoil effect
  • Nanomaterials
  • Carriers
  • Radiopharmacy
  • targeted alpha therapy
  • TAT

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Published Papers (3 papers)

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Research

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17 pages, 4706 KiB  
Article
A Novel Single-Step-Labeled 212Pb-CaCO3 Microparticle for Internal Alpha Therapy: Preparation, Stability, and Preclinical Data from Mice
by Ruth Gong Li, Kim Lindland, Tina Bjørnlund Bønsdorff, Sara Westrøm and Roy Hartvig Larsen
Materials 2021, 14(23), 7130; https://doi.org/10.3390/ma14237130 - 23 Nov 2021
Cited by 5 | Viewed by 2971
Abstract
Lead-212 is recognized as a promising radionuclide for targeted alpha therapy for tumors. Many studies of 212Pb-labeling of various biomolecules through bifunctional chelators have been conducted. Another approach to exploiting the cytotoxic effect is coupling the radionuclide to a microparticle acting as [...] Read more.
Lead-212 is recognized as a promising radionuclide for targeted alpha therapy for tumors. Many studies of 212Pb-labeling of various biomolecules through bifunctional chelators have been conducted. Another approach to exploiting the cytotoxic effect is coupling the radionuclide to a microparticle acting as a carrier vehicle, which could be used for treating disseminated cancers in body cavities. Calcium carbonate may represent a suitable material, as it is biocompatible, biodegradable, and easy to synthesize. In this work, we explored 212Pb-labeling of various CaCO3 microparticles and developed a protocol that can be straightforwardly implemented by clinicians. Vaterite microparticles stabilized by pamidronate were effective as 212Pb carriers; labeling yields of ≥98% were achieved, and 212Pb was strongly retained by the particles in an in vitro stability assessment. Moreover, the amounts of 212Pb reaching the kidneys, liver, spleen, and skeleton of mice following intraperitoneal (i.p.) administration were very low compared to i.p. injection of unbound 212Pb2+, indicating that CaCO3-bound 212Pb exhibited stability when administered intraperitoneally. Therapeutic efficacy was observed in a model of i.p. ovarian cancer for all the tested doses, ranging from 63 to 430 kBq per mouse. Lead-212-labeled CaCO3 microparticles represent a promising candidate for treating intracavitary cancers. Full article
(This article belongs to the Special Issue Advanced Systems in Targeted Alpha Particle Therapy)
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9 pages, 495 KiB  
Article
Determination, Modeling and Evaluation of Kinetics of 223Ra Sorption on Hydroxyapatite and Titanium Dioxide Nanoparticles
by Petra Suchánková, Ekaterina Kukleva, Karel Štamberg, Pavel Nykl, Michal Sakmár, Martin Vlk and Ján Kozempel
Materials 2020, 13(8), 1915; https://doi.org/10.3390/ma13081915 - 19 Apr 2020
Cited by 18 | Viewed by 2319
Abstract
Sorption kinetics of radium on hydroxyapatite and titanium dioxide nanomaterials were studied. The main aim of the current study was to determine the rate-controlling process and the corresponding kinetic model, due to the application of studied nanomaterials as α-emitters’ carriers, and to assess [...] Read more.
Sorption kinetics of radium on hydroxyapatite and titanium dioxide nanomaterials were studied. The main aim of the current study was to determine the rate-controlling process and the corresponding kinetic model, due to the application of studied nanomaterials as α-emitters’ carriers, and to assess the sorption properties of both materials from the radiopharmaceutical point of view by time regulated sorption experiments on the nanoparticles. Radium-223 was investigated as radionuclide used in targeted alpha particle therapy as an in vivo generator. It was found that the controlling process of the 223Ra sorption kinetics was the diffusion in a reacted layer. Therefore, parameters like particle size, their specific surface area, contact time and temperature played important role. Moreover, the composition of liquid phase, such as pH, the concentration of 223Ra, ionic strength, the presence of complexation ligands, etc., had to be considered. Experiments were conducted under free air conditions and at pH 8 for hydroxyapatite and pH 6 for titanium dioxide in Britton–Robinson buffer. Initial 223Ra concentration was in the range from 10−11 to 10−12 mol/L. It was found that sorption kinetics was very fast (more than 90% in the first hour) in the case of both nanomaterials, so they can be directly used for efficient radium sorption. Full article
(This article belongs to the Special Issue Advanced Systems in Targeted Alpha Particle Therapy)
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Review

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17 pages, 24450 KiB  
Review
Obstacles and Recommendations for Clinical Translation of Nanoparticle System-Based Targeted Alpha-Particle Therapy
by Janke Kleynhans, Mike Sathekge and Thomas Ebenhan
Materials 2021, 14(17), 4784; https://doi.org/10.3390/ma14174784 - 24 Aug 2021
Cited by 21 | Viewed by 3847
Abstract
The rationale for application of nanotechnology in targeted alpha therapy (TAT) is sound. However, the translational strategy requires attention. Formulation of TAT in nanoparticulate drug delivery systems has the potential to resolve many of the issues currently experienced. As α-particle emitters are more [...] Read more.
The rationale for application of nanotechnology in targeted alpha therapy (TAT) is sound. However, the translational strategy requires attention. Formulation of TAT in nanoparticulate drug delivery systems has the potential to resolve many of the issues currently experienced. As α-particle emitters are more cytotoxic compared to beta-minus-emitting agents, the results of poor biodistribution are more dangerous. Formulation in nanotechnology is also suggested to be the ideal solution for containing the recoil daughters emitted by actinium-225, radium-223, and thorium-227. Nanoparticle-based TAT is likely to increase stability, enhance radiation dosimetry profiles, and increase therapeutic efficacy. Unfortunately, nanoparticles have their own unique barriers towards clinical translation. A major obstacle is accumulation in critical organs such as the spleen, liver, and lungs. Furthermore, inflammation, necrosis, reactive oxidative species, and apoptosis are key mechanisms through which nanoparticle-mediated toxicity takes place. It is important at this stage of the technology’s readiness level that focus is shifted to clinical translation. The relative scarcity of α-particle emitters also contributes to slow-moving research in the field of TAT nanotechnology. This review describes approaches and solutions which may overcome obstacles impeding nanoparticle-based TAT and enhance clinical translation. In addition, an in-depth discussion of relevant issues and a view on technical and regulatory barriers are presented. Full article
(This article belongs to the Special Issue Advanced Systems in Targeted Alpha Particle Therapy)
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