scholarly journals Targeted Alpha Therapy: Progress in Radionuclide Production, Radiochemistry, and Applications

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 49
Author(s):  
Bryce Nelson ◽  
Jan Andersson ◽  
Frank Wuest
Keyword(s):  
Clinical Trials ◽  
Particle Therapy ◽  
Particle Emissions ◽  
Targeted Alpha Therapy ◽  
Radionuclide Production ◽  
Decay Properties ◽  
Superior Efficacy ◽  
The Future ◽  
Production Techniques ◽  
Alpha Therapy

This review outlines the accomplishments and potential developments of targeted alpha (α) particle therapy (TAT). It discusses the therapeutic advantages of the short and highly ionizing path of α-particle emissions; the ability of TAT to complement and provide superior efficacy over existing forms of radiotherapy; the physical decay properties and radiochemistry of common α-emitters, including 225Ac, 213Bi, 224Ra, 212Pb, 227Th, 223Ra, 211At, and 149Tb; the production techniques and proper handling of α-emitters in a radiopharmacy; recent preclinical developments; ongoing and completed clinical trials; and an outlook on the future of TAT.

scholarly journals Manual on the proper use of sodium astatide ([211At]NaAt) injections in clinical trials for targeted alpha therapy (1st edition)

2021 ◽  
Author(s):  
Tadashi Watabe ◽  
Makoto Hosono ◽  
Seigo Kinuya ◽  
Takahiro Yamada ◽  
Sachiko Yanagida ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Japanese Society ◽  
Radiation Safety ◽  
Safety Management ◽  
Evaluation Methodology ◽  
Targeted Alpha Therapy ◽  
Safety Issues ◽  
Safety Standards ◽  
And Training ◽  
Alpha Therapy

AbstractWe present the guideline for use of [211At] sodium astatide (NaAt) for targeted alpha therapy in clinical trials on the basis of radiation safety issues in Japan. This guideline was prepared by a study supported by the Ministry of Health, Labour, and Welfare, and approved by the Japanese Society of Nuclear Medicine on 8th Feb, 2021. The study showed that patients receiving [211At]NaAt do not need to be admitted to a radiotherapy room and outpatient treatment is possible. The radiation exposure from the patient is within the safety standards of the ICRP and IAEA recommendations for the general public and caregivers. Precautions for patients and their families, safety management associated with the use of [211At]NaAt, education and training, and disposal of medical radioactive contaminants are also included in this guideline. Treatment using [211At]NaAt in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection and evaluation methodology shown here are considered internationally useful as well.

New Directions for Clinical Trials of Targeted Alpha Therapy for Metastatic Melanoma

2008 ◽  
Vol 1 (3) ◽  
pp. 240-250 ◽  
Author(s):  
Barry Allen ◽  
Chand Raja ◽  
Syed Rizvi ◽  
Peter Graham ◽  
John Kearsley
Keyword(s):  
Clinical Trials ◽  
Metastatic Melanoma ◽  
Targeted Alpha Therapy ◽  
New Directions ◽  
Alpha Therapy

scholarly journals The Potential and Hurdles of Targeted Alpha Therapy – Clinical Trials and Beyond

2014 ◽  
Vol 3 ◽  
Author(s):  
Jörgen Elgqvist ◽  
Sofia Frost ◽  
Jean-Pierre Pouget ◽  
Per Albertsson
Keyword(s):  
Clinical Trials ◽  
Targeted Alpha Therapy ◽  
Alpha Therapy

scholarly journals 212Pb: Production Approaches and Targeted Therapy Applications

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 189
Author(s):  
Konstantin V. Kokov ◽  
Bayirta V. Egorova ◽  
Marina N. German ◽  
Ilya D. Klabukov ◽  
Michael E. Krasheninnikov ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Preclinical Studies ◽  
Clinical Implementation ◽  
Minimum Loss ◽  
Targeted Alpha Therapy ◽  
High Effectiveness ◽  
Alpha Emitter ◽  
Oncological Diseases ◽  
Parent Radionuclide ◽  
Alpha Therapy

Over the last decade, targeted alpha therapy has demonstrated its high effectiveness in treating various oncological diseases. Lead-212, with a convenient half-life of 10.64 h, and daughter alpha-emitter short-lived 212Bi (T1/2 = 1 h), provides the possibility for the synthesis and purification of complex radiopharmaceuticals with minimum loss of radioactivity during preparation. As a benefit for clinical implementation, it can be milked from a radionuclide generator in different ways. The main approaches applied for these purposes are considered and described in this review, including chromatographic, solution, and other techniques to isolate 212Pb from its parent radionuclide. Furthermore, molecules used for lead’s binding and radiochemical features of preparation and stability of compounds labeled with 212Pb are discussed. The results of preclinical studies with an estimation of therapeutic and tolerant doses as well as recently initiated clinical trials of targeted radiopharmaceuticals are presented.

scholarly journals Autoradiography Imaging in Targeted Alpha Therapy with Timepix Detector

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ruqaya AL Darwish ◽  
Alexander Hugo Staudacher ◽  
Eva Bezak ◽  
Michael Paul Brown
Keyword(s):  
Alpha Particle ◽  
Radiation Detector ◽  
Absorbed Dose ◽  
Compartmental Analysis ◽  
Alpha Particles ◽  
Imaging Data ◽  
Analysis Model ◽  
Particle Emissions ◽  
Targeted Alpha Therapy ◽  
Alpha Therapy

There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB), with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy.

Bridging the Knowledge Gaps in Arrhythmogenic Cardiovascular Conditions: The Critical Role of Registries

2016 ◽  
Vol 10 (2) ◽  
pp. 1 ◽  
Author(s):  
Melody Hermel ◽  
Rebecca Duffy ◽  
Alexander Orfanos ◽  
Isabelle Hack ◽  
Shayna McEnteggart ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Risk Stratification ◽  
Critical Role ◽  
Knowledge Gaps ◽  
Level Of Evidence ◽  
The Future

Cardiac registries have filled many gaps in knowledge related to arrhythmogenic cardiovascular conditions. Despite the less robust level of evidence available in registries when compared with clinical trials, registries have contributed a range of clinically useful information. In this review, the authors discuss the role that registries have played – related to diagnosis, natural history, risk stratification, treatment, and genetics of arrhythmogenic cardiovascular conditions – in closing knowledge gaps, and their role in the future.

Nanoconstructs in Targeted Alpha-Therapy

2015 ◽  
Vol 4 (2) ◽  
pp. 71-76 ◽  
Author(s):  
Jan Kozempel ◽  
Martin Vlk
Keyword(s):  
Targeted Alpha Therapy ◽  
Alpha Therapy

scholarly journals Exploring new uses for existing drugs: innovative mechanisms to fund independent clinical research

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ciska Verbaanderd ◽  
Ilse Rooman ◽  
Isabelle Huys
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Financial Support ◽  
Social Impact ◽  
Grey Literature ◽  
Economic Incentives ◽  
Phase Iii ◽  
Medical Needs ◽  
The Future ◽  
Funding Mechanisms

Abstract Background Finding new therapeutic uses for existing medicines could lead to safe, affordable and timely new treatment options for patients with high medical needs. However, due to a lack of economic incentives, pharmaceutical developers are rarely interested to invest in research with approved medicines, especially when they are out of basic patent or regulatory protection. Consequently, potential new uses for these medicines are mainly studied in independent clinical trials initiated and led by researchers from academia, research institutes, or collaborative groups. Yet, additional financial support is needed to conduct expensive phase III clinical trials to confirm the results from exploratory research. Methods In this study, scientific and grey literature was searched to identify and evaluate new mechanisms for funding clinical trials with repurposed medicines. Semi-structured interviews were conducted with 16 European stakeholders with expertise in clinical research, funding mechanisms and/or drug repurposing between November 2018 and February 2019 to consider the future perspectives of applying new funding mechanisms. Results Traditional grant funding awarded by government and philanthropic organisations or companies is well known and widely implemented in all research fields. In contrast, only little research has focused on the application potential of newer mechanisms to fund independent clinical research, such as social impact bonds, crowdfunding or public-private partnerships. Interviewees stated that there is a substantial need for additional financial support in health research, especially in areas where there is limited commercial interest. However, the implementation of new funding mechanisms is facing several practical and financial challenges, such as a lack of expertise and guidelines, high transaction costs and difficulties to measure health outcomes. Furthermore, interviewees highlighted the need for increased collaboration and centralisation at a European and international level to make clinical research more efficient and reduce the need for additional funding. Conclusions New funding mechanisms to support clinical research may become more important in the future but the unresolved issues identified in the current study warrant further exploration.

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