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Current Radiopharmaceuticals 2018Recent reports of the remarkable therapeutic efficacy of 225Ac-labeled PSMA- 617 for therapy of metastatic castration-resistant prostate cancer have underlined the... (Review)
Review
BACKGROUND
Recent reports of the remarkable therapeutic efficacy of 225Ac-labeled PSMA- 617 for therapy of metastatic castration-resistant prostate cancer have underlined the clinical potential of targeted alpha therapy.
OBJECTIVE AND CONCLUSION
This review describes methods for the production of 225Ac and its daughter nuclide 213Bi and summarizes the current clinical experience with both alpha emitters with particular focus on recent studies of targeted alpha therapy of bladder cancer, brain tumors, neuroendocrine tumors and prostate cancer.
Topics: Actinium; Alpha Particles; Bismuth; Clinical Trials as Topic; Humans; Neoplasms; Radiochemistry; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals
PubMed: 29732998
DOI: 10.2174/1874471011666180502104524 -
Frontiers in Oncology 2021Boron neutron capture therapy (BNCT) is an emerging treatment modality aimed at improving the therapeutic ratio for traditionally difficult to treat tumors. BNCT... (Review)
Review
Boron neutron capture therapy (BNCT) is an emerging treatment modality aimed at improving the therapeutic ratio for traditionally difficult to treat tumors. BNCT utilizes boronated agents to preferentially deliver boron-10 to tumors, which, after undergoing irradiation with neutrons, yields litihium-7 and an alpha particle. The alpha particle has a short range, therefore preferentially affecting tumor tissues while sparing more distal normal tissues. To date, BNCT has been studied clinically in a variety of disease sites, including glioblastoma multiforme, meningioma, head and neck cancers, lung cancers, breast cancers, hepatocellular carcinoma, sarcomas, cutaneous malignancies, extramammary Paget's disease, recurrent cancers, pediatric cancers, and metastatic disease. We aim to provide an up-to-date and comprehensive review of the studies of each of these disease sites, as well as a review on the challenges facing adoption of BNCT.
PubMed: 33718149
DOI: 10.3389/fonc.2021.601820 -
Journal of Nuclear Medicine : Official... Dec 2016Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide-labeled...
UNLABELLED
Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide-labeled PSMA ligand. Although the case series is still ongoing, we here report in advance about two patients in highly challenging clinical situations who showed a complete response to Ac-PSMA-617 therapy.
METHODS
Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq activity of Ac-PSMA-617 per kilogram of body weight was administered bimonthly. Prostate-specific antigen response and hematologic toxicity were measured at least every 4 wk. Restaging was performed with Ga-PSMA-11 PET/CT.
RESULTS
Both patients experienced a prostate-specific antigen decline to below the measurable level and showed a complete response on imaging. No relevant hematologic toxicity was observed. Xerostomia was the only mentionable clinical side effect.
CONCLUSION
Targeted α-therapy with Ac-PSMA-617, although still experimental, obviously has strong potential to significantly benefit advanced-stage prostate cancer patients.
Topics: Actinium; Alpha Particles; Antigens, Surface; Beta Particles; Dipeptides; Glutamate Carboxypeptidase II; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Neoplasm Metastasis; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes
PubMed: 27390158
DOI: 10.2967/jnumed.116.178673 -
International Journal of Molecular... Jul 2023Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as... (Review)
Review
Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as catalysts. Targeted alpha emitters are in current development for several potential oncologic indications. Herein, we review the three most prevalently studied conjugated/chelated alpha emitters (actinium, lead, and astatine) and focus on contemporary clinical trials in an effort to more fully appreciate the breadth of the current evaluation. Phase I trials targeting multiple diseases are now underway, and at least one phase III trial (in selected neuroendocrine cancers) is currently in the initial stages of recruitment. Combination trials are now also emerging as alpha emitters are integrated with other therapies in an effort to create solutions for those with advanced cancers. Despite the promise of targeted alpha therapies, many challenges remain. These challenges include the development of reliable supply chains, the need for a better understanding of the relationships between administered dose and absorbed dose in both tissue and tumor and how that predicts outcomes, and the incomplete understanding of potential long-term deleterious effects of the alpha emitters. Progress on multiple fronts is necessary to bring the potential of targeted alpha therapies into the clinic.
Topics: Humans; Male; Alpha Particles; Prostatic Neoplasms; Radiopharmaceuticals; Clinical Trials as Topic
PubMed: 37511386
DOI: 10.3390/ijms241411626 -
European Journal of Nuclear Medicine... May 2018Radium Ra-223 dichloride (radium-223, Xofigo®) is a targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with symptomatic...
Radium Ra-223 dichloride (radium-223, Xofigo®) is a targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is the first targeted alpha therapy in this indication providing a new treatment option, with evidence of a significant survival benefit, both in overall survival and in the time to the first symptomatic skeletal-related event. The skeleton is the most common metastatic site in patients with advanced prostate cancer. Bone metastases are a clinically significant cause of morbidity and mortality, often resulting in bone pain, pathologic fracture, or spinal cord compression necessitating treatment. Radium-223 is selectively accumulated in the bone, specifically in areas of high bone turnover, by forming complexes with the mineral hydroxyapatite (the inorganic matrix of the bone). The alpha radiation generated during the radioactive decay of radium-223 produces a palliative anti-tumour effect on the bone metastases. The purpose of this guideline is to assist nuclear medicine specialists in evaluating patients who might be candidates for treatment using radium-223, planning and performing this treatment, understanding and evaluating its consequences, and improving patient management during therapy and follow-up.
Topics: Bone Neoplasms; Europe; Humans; Male; Practice Guidelines as Topic; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radium
PubMed: 29234845
DOI: 10.1007/s00259-017-3900-4 -
Toxics Aug 2023Radon is a carcinogenic factor, but the effects of the potential carcinogenicity of radon progeny on the human body during the prenatal period have not yet been...
Radon is a carcinogenic factor, but the effects of the potential carcinogenicity of radon progeny on the human body during the prenatal period have not yet been explored. Based on data regarding the half-lives of radon-222 and radon-220 and their progeny, this paper considers their potential effects on the human body in the prenatal period. Radon-220 represents a small fraction of the total radon concentration in the air, but the dose of radon-220 progeny may have a significant effect in the prenatal period, as the precursors of polonium-212 exhibit substantially longer half-lives than the corresponding precursors of polonium-214. Theoretically, it is possible that radon-220 decay products, particularly polonium-212, are the predominant emitters of alpha particles in the prenatal period. Studies aiming to establish a relationship between exposure to radon during pregnancy and the subsequently observed incidence of childhood neoplasms should consider this observation.
PubMed: 37624186
DOI: 10.3390/toxics11080681 -
Annual Review of Biomedical Engineering Jun 2018α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of... (Review)
Review
α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of α-particle emitters, as well as the distinguishing features that make them unique for radiopharmaceutical therapy. We also review the emerging clinical role of α-particle therapy in managing cancer and recent studies on in vitro and preclinical α-particle therapy delivered by antibodies, other small molecules, and nanometer-sized particles. In addition to their unique radiopharmaceutical characteristics, the increased availability and improved radiochemistry of α-particle radionuclides have contributed to the growing recent interest in α-particle radiotherapy. Targeted therapy strategies have presented novel possibilities for the use of α-particles in the treatment of cancer. Clinical experience has already demonstrated the safe and effective use of α-particle emitters as potent tumor-selective drugs for the treatment of leukemia and metastatic disease.
Topics: Actinium; Alpha Particles; Animals; Cell Survival; Clinical Trials as Topic; Drug Carriers; Humans; Kinetics; Leukemia; Nanomedicine; Nanoparticles; Neoplasm Metastasis; Neoplasms; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals; Radium
PubMed: 29345977
DOI: 10.1146/annurev-bioeng-062117-120931