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Special Issue "Advanced Systems in Targeted Alpha Particle Therapy"

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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 6410

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Special Issue Editor

Prof. Ján Kozempel

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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

Published Papers (3 papers)

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Research

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17 pages, 4706 KiB

Open AccessArticle

A Novel Single-Step-Labeled ²¹²Pb-CaCO₃ Microparticle for Internal Alpha Therapy: Preparation, Stability, and Preclinical Data from Mice

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 2 | Viewed by 1809

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 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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Graphical abstract

9 pages, 495 KiB

Open AccessArticle

Determination, Modeling and Evaluation of Kinetics of ²²³Ra Sorption on Hydroxyapatite and Titanium Dioxide Nanoparticles

and

Materials 2020, 13(8), 1915; https://doi.org/10.3390/ma13081915 - 19 Apr 2020

Cited by 11 | Viewed by 1682

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 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

Open AccessReview

Obstacles and Recommendations for Clinical Translation of Nanoparticle System-Based Targeted Alpha-Particle Therapy

Janke Kleynhans

Mike Sathekge

and

Thomas Ebenhan

Materials 2021, 14(17), 4784; https://doi.org/10.3390/ma14174784 - 24 Aug 2021

Cited by 11 | Viewed by 2336

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 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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