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Journal of Medical Imaging and... Dec 2019This talk briefly reviews the earlier work in the field and highlights the contributions of colleagues whose clear vision paved the road for success of TAT. The talk... (Review)
Review
This talk briefly reviews the earlier work in the field and highlights the contributions of colleagues whose clear vision paved the road for success of TAT. The talk primarily will focus on the development of the radioisotopes for application in TAT. The challenges regarding release of daughter radioisotopes will be briefly discussed, and a summary of the alternative approaches for production of Ac will be presented.
Topics: Actinium; Alpha Particles; Humans; Neoplasms; Radioisotopes; Radiotherapy
PubMed: 31420270
DOI: 10.1016/j.jmir.2019.07.002 -
Seminars in Nuclear Medicine Mar 2020Prostate-specific membrane antigen (PSMA)-targeting radio-ligand therapy with beta-emitting Lutetium has already been investigated in several early phase dosimetry... (Review)
Review
Prostate-specific membrane antigen (PSMA)-targeting radio-ligand therapy with beta-emitting Lutetium has already been investigated in several early phase dosimetry studies, demonstrated promising results in phase-2, and recently the first phase-3 trial finished recruitment. In contrast, PSMA-targeting alpha-particle therapy (TAT) has only been evaluated in few preclinical experiments, preliminary dosimetry attempts and some retrospective observational studies, yet. First clinical experience with Ac-PSMA-617 demonstrates promising antitumor activity with a 63%-70% PSA-response rate, 10-15 months duration of response and complete remissions in approximately ten percent of patients, some of them with enduring relapse-free survival. Nevertheless, without comparative trials there is no prove whether, applied in identical clinical situations, Ac-PSMA-617 is really more efficiently than Lu-PSMA-617 or vice versa. However, there is some good rationale, that PSMA-TAT might have advantages in particular clinical indications. This includes patients with diffuse type red-marrow infiltration by reducing off-target radiation to surrounding cells; ablation of micrometastases after favorable response to other previous therapy or someday in early stage disease. Also treatment escalation of patients, either with poor response to Lu-PSMA or harboring adverse prognostic biomarkers, appears promising. In preclinical research, alpha-radiation demonstrated stronger induction of abscopal effects than beta-radiation; favoring its usage as a combination partner with immunotherapies. So, further evaluation of PSMA-TAT is definitely warranted. Recently, de-escalated treatment protocols and application of Ac/Lu-PSMA "cocktail"-regimens improved the tolerability of Ac-PSMA-617 TAT, reducing the risk for development dry-mouth syndrome. This opens new avenues for future application in earlier stage disease.
Topics: Actinium; Alpha Particles; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Safety
PubMed: 32172798
DOI: 10.1053/j.semnuclmed.2020.02.004 -
PET Clinics Jul 2024Peptide receptor radionuclide therapy (PRRT) has become mainstream therapy of metastatic neuroendocrine tumors not controlled by somatostatin analog therapy. Currently,... (Review)
Review
Peptide receptor radionuclide therapy (PRRT) has become mainstream therapy of metastatic neuroendocrine tumors not controlled by somatostatin analog therapy. Currently, beta particle-emitting radiopharmaceuticals are the mainstay of PRRT. Alpha particle-emitting radiopharmaceuticals have a theoretic advantage over beta emitters in terms of improved therapeutic efficacy due to higher cancer cell death and lower nontarget tissue radiation-induced adverse events due to shorter path length of alpha particles. We discuss the available evidence for and the role of alpha particle PRRT.
Topics: Humans; Neuroendocrine Tumors; Radiopharmaceuticals; Alpha Particles; Receptors, Peptide; Octreotide; Radioisotopes
PubMed: 38658229
DOI: 10.1016/j.cpet.2024.03.005 -
Assay and Drug Development Technologies Oct 2010Alpha-particle-emitting elements are of increasing importance as environmental and occupational carcinogens, toxic components of radiation dispersal devices and...
Alpha-particle-emitting elements are of increasing importance as environmental and occupational carcinogens, toxic components of radiation dispersal devices and accidents, and potent therapeutics in oncology. Alpha particle radiation differs from radiations of lower linear energy transfer in that it predominantly damages DNA via direct action. Because of this, radical scavengers effective for other radiations have had only limited effect in mitigating alpha particle toxicity. We describe here a simple assay and a pilot screen of 3,119 compounds in a high-throughput screen (HTS), using the alpha-particle-emitting isotope, ²²⁵Ac, for the discovery of compounds that might protect mammalian cells from alpha particles through novel mechanisms. The assay, which monitored the viability of a myeloid leukemic cell line upon alpha particle exposure, was robust and reproducible, yielding a Z' factor of 0.66 and a signal-to-noise ratio of nearly 10 to 1. Surprisingly, 1 compound emerged from this screen, epoxy-4,5-α-dihydroxysantonin (EDHS), that showed considerable protective activity. While the value of EDHS remains to be determined, its discovery is a proof of concept and validation of the utility of this HTS methodology. Further application of the described assay could yield compounds useful in minimizing the toxicity and carcinogenesis associated with alpha particle exposure.
Topics: Alpha Particles; Aluminum Compounds; Cell Line, Tumor; DNA Damage; Drug Evaluation, Preclinical; HL-60 Cells; High-Throughput Screening Assays; Humans; Nitrates; Radiation-Protective Agents; Reproducibility of Results; Small Molecule Libraries
PubMed: 20658946
DOI: 10.1089/adt.2010.0291 -
Health Physics Sep 1992Historically, alpha-particle detectors have been limited by the very short range of alpha particles in air. This results in a number of problems inherent to alpha...
Historically, alpha-particle detectors have been limited by the very short range of alpha particles in air. This results in a number of problems inherent to alpha contamination detectors, such as relatively poor sensitivity, geometry limitations, and inefficient monitoring techniques. In this paper, we document tests of a new long-range alpha detector. The charges generated by the interaction of alpha particles with air can be transported over significant distances (several meters) in a moving current of air generated by a small fan. An ion chamber located in front of the fan measures the current carried by the moving ions and, hence, detects the alpha decays.
Topics: Alpha Particles; Environmental Monitoring; Radiation Monitoring; Radiometry
PubMed: 1644569
DOI: 10.1097/00004032-199209000-00008 -
International Journal of Radiation... Dec 1998
Review
Topics: Alpha Particles; Animals; Cell Division; Cell Line; Chromosomes; DNA Damage; Genome; Mammals; Radiation, Ionizing; Reproduction; X-Rays
PubMed: 9881710
DOI: 10.1080/095530098140925 -
Critical Reviews in Oncology/hematology Mar 2018Targeted therapy for cancer is a rapidly expanding and successful approach to the management of many intractable cancers. However, many immunotherapies fail in the... (Review)
Review
Targeted therapy for cancer is a rapidly expanding and successful approach to the management of many intractable cancers. However, many immunotherapies fail in the longer term and there continues to be a need for improved targeted cancer cell toxicity, which can be achieved by radiolabelling the targeting vector with a radioisotope. Such constructs are successful in using a gamma ray emitter for imaging. However, traditionally, a beta emitter is used for therapeutic applications. The new approach is to use the short range and highly cytotoxic alpha radiation from alpha emitters to achieve improved efficacy and therapeutic gain. This paper sets out to review all experimental and theoretical comparisons of efficacy and therapeutic gain for alpha and beta emitters labelling the same targeting vector. The overall conclusion is that targeted alpha therapy is superior to targeted beta therapy, such that the use of alpha therapy in clinical settings should be expanded.
Topics: Alpha Particles; Animals; Beta Particles; Cancer Pain; Cells, Cultured; Clinical Trials as Topic; Humans; Neoplasms; Radioisotopes; Radiotherapy
PubMed: 29482781
DOI: 10.1016/j.critrevonc.2018.01.001 -
Mutation Research Jan 2013The goal of this study was to compare the cytotoxic and genotoxic effects of plutonium-239 alpha particles and GSM 900 modulated mobile phone (model Sony Ericsson K550i)... (Comparative Study)
Comparative Study
The goal of this study was to compare the cytotoxic and genotoxic effects of plutonium-239 alpha particles and GSM 900 modulated mobile phone (model Sony Ericsson K550i) radiation in the Allium cepa test. Three groups of bulbs were exposed to mobile phone radiation during 0 (sham), 3 and 9h. A positive control group was treated during 20min with plutonium-239 alpha-radiation. Mitotic abnormalities, chromosome aberrations, micronuclei and mitotic index were analyzed. Exposure to alpha-radiation from plutonium-239 and exposure to modulated radiation from mobile phone during 3 and 9h significantly increased the mitotic index. GSM 900 mobile phone radiation as well as alpha-radiation from plutonium-239 induced both clastogenic and aneugenic effects. However, the aneugenic activity of mobile phone radiation was more pronounced. After 9h of exposure to mobile phone radiation, polyploid cells, three-groups metaphases, amitoses and some unspecified abnormalities were detected, which were not registered in the other experimental groups. Importantly, GSM 900 mobile phone radiation increased the mitotic index, the frequency of mitotic and chromosome abnormalities, and the micronucleus frequency in a time-dependent manner. Due to its sensitivity, the A. cepa test can be recommended as a useful cytogenetic assay to assess cytotoxic and genotoxic effects of radiofrequency electromagnetic fields.
Topics: Alpha Particles; Cell Phone; Chromosome Aberrations; DNA Damage; Electromagnetic Radiation; Micronuclei, Chromosome-Defective; Mitotic Index; Onions; Plutonium
PubMed: 23059817
DOI: 10.1016/j.mrgentox.2012.08.010 -
Antimicrobial Agents and Chemotherapy 2014Radioimmunotherapy (RIT) takes advantage of the specificity and affinity of the antigen-antibody interaction to deliver microbicidal radioactive nuclides to a site of...
Radioimmunotherapy (RIT) takes advantage of the specificity and affinity of the antigen-antibody interaction to deliver microbicidal radioactive nuclides to a site of infection. In this study, we investigated the microbicidal properties of an alpha particle-emitting 213Bi-labeled monoclonal antibody (MAb), EA2-1 (213Bi-EA2-1), that binds to the immunodominant antigen on Bacillus anthracis spores. Our results showed that dormant spores were resistant to 213Bi-EA2-1. Significant spore killing was observed following treatment with EA2-1 labeled with 300 μCi 213Bi; however, this effect was not dependent on the MAb. In contrast, when spores were germinating, 213Bi-EA2-1 mediated MAb-specific killing in a dose-dependent manner. Dormant spores are very resistant to RIT, and RIT should focus on targeting vegetative cells and germinating spores.
Topics: Alpha Particles; Antibodies, Monoclonal; Bacillus anthracis; Bismuth; Microscopy, Phase-Contrast; Radioisotopes; Spores, Bacterial
PubMed: 24379209
DOI: 10.1128/AAC.01266-13 -
Nuclear Medicine and Biology 2022Lanthanum radiometals are well positioned to serve as theranostic PET radiometals for targeted radionuclide therapy. The positron emitters La and La show promise to... (Review)
Review
Lanthanum radiometals are well positioned to serve as theranostic PET radiometals for targeted radionuclide therapy. The positron emitters La and La show promise to serve as unique PET imaging agents for Ac targeted alpha-particle therapy, the Ce/La pair has PET imaging potential with both Ac and Th, and La has potential in targeted Auger-Meitner electron therapy. With easily accessible cyclotron production routes, effective and efficient chemical separations, and robust chelation chemistry, these radionuclides are well poised for additional preclinical and clinical PET and targeted radionuclide therapy studies. This review summarizes recent advances in radiolanthanum production and preclinical applications that demonstrate the strong potential of these radionuclides in PET and targeted radionuclide therapy.
Topics: Alpha Particles; Cyclotrons; Positron-Emission Tomography; Precision Medicine; Radioisotopes
PubMed: 35487834
DOI: 10.1016/j.nucmedbio.2022.04.005