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Pharmaceutics Jun 2023The actinium-225 (Ac) radioisotope exhibits highly attractive nuclear properties for application in radionuclide therapy. However, the Ac radionuclide presents multiple... (Review)
Review
The actinium-225 (Ac) radioisotope exhibits highly attractive nuclear properties for application in radionuclide therapy. However, the Ac radionuclide presents multiple daughter nuclides in its decay chain, which can escape the targeted site, circulate in plasma, and cause toxicity in areas such as kidneys and renal tissues. Several ameliorative strategies have been devised to circumvent this issue, including nano-delivery. Alpha-emitting radionuclides and nanotechnology applications in nuclear medicine have culminated in major advancements that offer promising therapeutic possibilities for treating several cancers. Accordingly, the importance of nanomaterials in retaining the Ac daughters from recoiling into unintended organs has been established. This review expounds on the advancements of targeted radionuclide therapy (TRT) as an alternative anticancer treatment. It discusses the recent developments in the preclinical and clinical investigations on Ac as a prospective anticancer agent. Moreover, the rationale for using nanomaterials in improving the therapeutic efficacy of α-particles in targeted alpha therapy (TAT) with an emphasis on Ac is discussed. Quality control measures in the preparation of Ac-conjugates are also highlighted.
PubMed: 37376167
DOI: 10.3390/pharmaceutics15061719 -
Annals of Oncology : Official Journal... Nov 2019Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor... (Review)
Review
Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment.
Topics: Actinium; Alpha Particles; Clinical Trials, Phase III as Topic; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Male; Precision Medicine; Progression-Free Survival; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunotherapy; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Tumor Microenvironment
PubMed: 31418764
DOI: 10.1093/annonc/mdz270 -
Frontiers in Medicine 2022Peptide receptor radionuclide therapy (PRRT) has over the last two decades emerged as a very promising approach to treat neuroendocrine tumors (NETs) with rapidly... (Review)
Review
Peptide receptor radionuclide therapy (PRRT) has over the last two decades emerged as a very promising approach to treat neuroendocrine tumors (NETs) with rapidly expanding clinical applications. By chelating a radiometal to a somatostatin receptor (SSTR) ligand, radiation can be delivered to cancer cells with high precision. Unlike conventional external beam radiotherapy, PRRT utilizes primarily β or α radiation derived from nuclear decay, which causes damage to cancer cells in the immediate proximity by irreversible direct or indirect ionization of the cells' DNA, which induces apoptosis. In addition, to avoid damage to surrounding normal cells, PRRT privileges the use of radionuclides that have little penetrating and more energetic (and thus more ionizing) radiations. To date, the most frequently radioisotopes are β emitters, particularly Yttrium-90 (Y) and Lutetium-177 (Lu), labeled SSTR agonists. Current development of SSTR-targeting is triggering the shift from using SSTR agonists to antagonists for PRRT. Furthermore, targeted α-particle therapy (TAT), has attracted special attention for the treatment of tumors and offers an improved therapeutic option for patients resistant to conventional treatments or even beta-irradiation treatment. Due to its short range and high linear energy transfer (LET), α-particles significantly damage the targeted cancer cells while causing minimal cytotoxicity toward surrounding normal tissue. Actinium-225 (Ac) has been developed into potent targeting drug constructs including somatostatin-receptor-based radiopharmaceuticals and is in early clinical use against multiple neuroendocrine tumor types. In this article, we give a review of preclinical and clinical applications of Ac-PRRT in NETs, discuss the strengths and challenges of Ac complexes being used in PRRT; and envision the prospect of Ac-PRRT as a future alternative in the treatment of NETs.
PubMed: 36569154
DOI: 10.3389/fmed.2022.1034315 -
Heliyon Mar 2021The current study determines the relationship between heavy metals and alpha particles emission rates in milk and blood of lactating women in Diwanyah, Iraq.
BACKGROUND
The current study determines the relationship between heavy metals and alpha particles emission rates in milk and blood of lactating women in Diwanyah, Iraq.
METHODS
Heavy metals and alpha particle emission rates have been measured using an Atomic Absorption Spectrophotometer and a Nuclear Track Detector.
RESULTS
The results show that Pb, Cd, and Cu in milk are 0.2239 ± 0.0007 ppm, 0.0156 ± 0.0001 ppm, and 0.1811 ± 0.0006 ppm, respectively. Pb, Cd, and Cu in the blood were 0.0898 ± 0.0008 ppm, 0.0432 ± 0.0010 ppm, and 0.1729 ± 0.0004 ppm, respectively. The highest alpha particle emission rate was found to be in age interval from 23 y to 28 y in milk, while the highest alpha particle emission rate was found to be in the age interval from 35 y to 40 y.
CONCLUSIONS
This study concludes that no statistical significance between Pb, Cd, Cu and Eα in milk and blood at level 0.01. The following order of bioavailability was found with heavy metals Cu < Pb < Cd.
PubMed: 33869840
DOI: 10.1016/j.heliyon.2021.e06590 -
Sensors (Basel, Switzerland) Jan 2022Nowadays, radon gas exposure is considered one of the main health concerns for the population because, by carrying about half the total dose due to environmental...
Nowadays, radon gas exposure is considered one of the main health concerns for the population because, by carrying about half the total dose due to environmental radioactivity, it is the second cause of lung cancer after smoking. Due to a relatively long half-life of 3.82 days, the chemical inertia and since its parent Ra-226 is largely diffuse on the earth's crust and especially in the building materials, radon can diffuse and potentially saturate human habitats, with a concentration that can suddenly change during the 24 h day depending on temperature, pressure, and relative humidity. For such reasons, 'real-time' measurements performed by an active detector, possibly of small dimensions and a handy configuration, can play an important role in evaluating the risk and taking the appropriate countermeasures to mitigate it. In this work, a novel algorithm for pattern recognition was developed to exploit the potentialities of silicon active detectors with a pixel matrix structure to measure radon through the emission, in a simple measurement configuration, where the device is placed directly in air with no holder, no collection filter or electrostatic field to drift the radon progenies towards the detector active area. This particular measurement configuration (dubbed as ) requires an /-discrimination method that is not based on spectroscopic analysis: as the gas surrounds the detector the particles are emitted at different distances from it, so they lose variable energy amount in air depending on the traveled path-length which implies a variable deposited energy in the active area. The pixels matrix structure allows overcoming this issue because the interaction of , and particles generate in the active area of the detector (group of pixels where a signal is read) of different shape and energy dispersion. The novel algorithm that exploits such a phenomenon was developed using a pixelated silicon detector of the TimePix family with a compact design. An (Am-241) and a (Sr-90) source were used to calibrate the algorithm and to evaluate its performances in terms of rejection capability and recognition efficiency. Successively, the detector was exposed to different radon concentrations at the ENEA-INMRI radon facility in 'bare' configuration, in order to check the linearity of the device response over a radon concentration range. The results for this technique are presented and discussed, highlighting the potential applications especially the possibility to exploit small and handy detectors to perform radon active measurements in the simplest configuration.
Topics: Air Pollutants, Radioactive; Algorithms; Humans; Radiation Monitoring; Radon; Radon Daughters
PubMed: 35062477
DOI: 10.3390/s22020516 -
Hellenic Journal of Nuclear Medicine 2023The first description of the in vivo visualization of somatostatin receptor-positive tumors in patients was based on the use of a radioiodine (I) labelled somatostatin...
The first description of the in vivo visualization of somatostatin receptor-positive tumors in patients was based on the use of a radioiodine (I) labelled somatostatin analogue (Krenning et al. 1989). In the years that followed an Indium-111 (In) labelled somatostatin analogue, chelated with diethylenetriaminepentaacetic acid (DTPA), was successfully developed. Subsequently, In-OctreoScan was introduced worldwide. In the years to come Tc-Tektrotyde became commercially available with easy access. In the last decade, with the increasing use of positron emission tomography (PET) imaging, somatostatin analogues have been labelled with various positron-emitting isotopes, such as Gallium-68 (Ga) and Copper-64 (Cu) (Lewis et al. 1999, Schottelius et al. 2004, Gabriel et al. 2007) e.g Ga-DOTATOC, Ga-DOTATATE Ga-DOTANOC and Cu-DOTATATE. Scintigraphy with these investigational compounds display encouraging good imaging quality amd improved sensitivity in tumor site detection compared with SPECT scintigraphy. Also, other PET radiopharmaceuticals were developed, such as F-dihydroxy-phenyl-alanine (F-DOPA) and C-labelled 5-hydroxytryptophan (C-5-HTP) with encouraging results in terms of visualization of GEP-NETs (Koopmans et al. 2008). After the successful introduction of SRS in the diagnosis and staging of NETs, the next logical step was to increase the administered activity so that the radiopharmaceutical can induce tumor shrinkage in patients who had inoperable and/or metastasized NENs. Therefore, the first peptide receptor radionuclide therapy (PRRT) was performed with high administered activity of [In-DTPA0] octreotide (Krenning et al. 1994a). To make significant advancements in the treatment of somatostatin receptor-positive metastatic disease, more efficient radiolabelled somatostatin analogues were developed with higher affinity to the somatostatin receptor. Treatment with radiolabelled peptides or PRRT is a promising new therapeutic option in the management of inoperable or metastasized NETs. Symptomatic control can be achieved with all In-, Y- and Lu-labelled somatostatin analogue-based PRRT. For objective response and long-lasting duration of response, Y-DOTATOC and Lu-DOTATATE are the most promising radiopharmaceuticals. Side effects of PRRT are few and mild, if adequate kidney protective measures are taken and dose-limits are respected. In a minority of patients, when SRS fails to identify neuroendocrine disease, MIBG scintigraphy and subsequent I-MBG therapy might be an alternative treatment option. Targeted alpha-particle therapy (TAT) has emerged as an alternative treatment option to beta emitters in PRRT. The use of alpha emitters for cancer therapy has two advantages over beta emitter PRRT. The short range of alpha particles of only a few cell diameters (<0.1mm) allows for selective ablation of the target cancer cells, while sparing the surrounding healthy tissue. In addition, the higher linear energy transfer (LET), when compared to conventional beta emitters, results in the formation of complex DNA double-strand and DNA cluster breaks, which ultimately lead to cell death.(Lassmann M et al. Ann ICRP. 2018) Putative radiopharmaceuticals that can be considered for metastatic NEN treatment include Actinium-225 (Ac)-DOTATATE and Bismuth-213 (Bi)-DOTATOC. There was evidence of partial response using both radiopharmaceutical agents without significant hematological, renal, or hepatotoxicity. Future studies should consider longer term, randomized controlled trials investigating the role of TAT, in particular, c-DOTATATE, in the treatment of metastatic NENs. Nuclear medicine plays a pivotal role in the imaging and treatment of neuroendocrine tumors (NETs). New techniques in somatostatin receptor imaging include the use of different radiolabelled somatostatin analogues with higher affinity and different affinity profiles to the somatostatin receptor subtypes. Considerable advances have been made in the imaging of NETs, but to find the ideal imaging method with increased sensitivity and better topographic localization of the primary and metastatic disease remains the ultimate goal of research.
Topics: Humans; Radiopharmaceuticals; Receptors, Somatostatin; Gallium Radioisotopes; Iodine Radioisotopes; Copper; Somatostatin; Pancreatic Neoplasms; Neuroendocrine Tumors; DNA; Organometallic Compounds
PubMed: 37658556
DOI: No ID Found -
Materials (Basel, Switzerland) Aug 2019In advanced fission and fusion reactors, structural materials suffer from high dose irradiation by energetic particles and are subject to severe microstructure damage.... (Review)
Review
In advanced fission and fusion reactors, structural materials suffer from high dose irradiation by energetic particles and are subject to severe microstructure damage. He atoms, as a byproduct of the (n, α) transmutation reaction, could accumulate to form deleterious cavities, which accelerate radiation-induced embrittlement, swelling and surface deterioration, ultimately degrade the service lifetime of reactor materials. Extensive studies have been performed to explore the strategies that can mitigate He ion irradiation damage. Recently, nanostructured materials have received broad attention because they contain abundant interfaces that are efficient sinks for radiation-induced defects. In this review, we summarize and analyze the current understandings on interface effects on He ion irradiation in nanostructured materials. Some key challenges and research directions are highlighted for studying the interface effects on radiation damage in nanostructured materials.
PubMed: 31430959
DOI: 10.3390/ma12162639 -
Oncology Reviews 2022Due to their electrostatic nature, radon decay products can attach to solid particles and aerosols in the air. Inhalation and ingestion are therefore the two main routes... (Review)
Review
Due to their electrostatic nature, radon decay products can attach to solid particles and aerosols in the air. Inhalation and ingestion are therefore the two main routes through which people are exposed to radon and its decay products. During the inhalation of these radioactive aerosols, deposition takes place in different regions of the human respiratory tract. The deposited aerosols carrying radon and its progeny undergo a continuous radioactive transformation and expose the lung to ionizing alpha radiation, which can destroy the sensitive cells in the lung, causing a mutation that turns cancerous. Radon which is a colorless, odorless, and tasteless radioactive noble gas is a major health concern and is the second leading cause of lung cancer. To address this, an indoor radon survey was conducted in many countries internationally, with results showing that indoor radon concentration has a seasonal variation. This is due to the fluctuation of environmental parameters and the geological nature of buildings. Its concentration was found to be maximum in the cool (winter) season and a minimum concentration was recorded in the warm (summer) season of the year.
PubMed: 36531161
DOI: 10.3389/or.2022.10570 -
Journal of Nuclear Medicine : Official... Oct 2022Ra is a bone-seeking, α-particle-emitting radionuclide approved for the treatment of patients with metastatic prostate cancer and is currently being tested in a variety...
Ra is a bone-seeking, α-particle-emitting radionuclide approved for the treatment of patients with metastatic prostate cancer and is currently being tested in a variety of clinical trials for primary and metastatic cancers to bone. Clinical evaluation of Ra hematologic safety showed a significantly increased rate of neutropenia and thrombocytopenia in patients, hinting at myelosuppression as a side effect. In this study, we investigated the consequences of Ra treatment on bone marrow biology by combining flow cytometry, single-cell RNA sequencing, three-dimensional multiphoton microscopy and bone marrow transplantation analyses. Ra accumulated in bones and induced zonal radiation damage confined to the bone interface, followed by replacement of the impaired areas with adipocyte infiltration, as monitored by 3-dimensional multiphoton microscopy ex vivo. Flow cytometry and single-cell transcriptomic analyses on bone marrow hematopoietic populations revealed transient, nonspecific Ra-mediated cytotoxicity on resident populations, including stem, progenitor, and mature leukocytes. This toxicity was paralleled by a significant decrease in white blood cells and platelets in peripheral blood-an effect that was overcome within 40 d after treatment. Ra exposure did not impair full hematopoietic reconstitution, suggesting that bone marrow function is not permanently hampered. Our results provide a comprehensive explanation of Ra reversible effects on bone marrow cells and exclude long-term myelotoxicity, supporting safety for patients.
Topics: Alpha Particles; Bone Marrow; Bone and Bones; Flow Cytometry; Humans; Male; Radioisotopes
PubMed: 35177425
DOI: 10.2967/jnumed.121.263310 -
Molecules (Basel, Switzerland) Apr 2021Bone metastasis remains a major cause of death in cancer patients, and current therapies for bone metastatic disease are mainly palliative. Bone metastases arise after... (Review)
Review
Bone metastasis remains a major cause of death in cancer patients, and current therapies for bone metastatic disease are mainly palliative. Bone metastases arise after cancer cells have colonized the bone and co-opted the normal bone remodeling process. In addition to bone-targeted therapies (e.g., bisphosphonate and denosumab), hormone therapy, chemotherapy, external beam radiation therapy, and surgical intervention, attempts have been made to use systemic radiotherapy as a means of delivering cytocidal radiation to every bone metastatic lesion. Initially, several bone-seeking beta-minus-particle-emitting radiopharmaceuticals were incorporated into the treatment for bone metastases, but they failed to extend the overall survival in patients. However, recent clinical trials indicate that radium-223 dichloride (RaCl), an alpha-particle-emitting radiopharmaceutical, improves the overall survival of prostate cancer patients with bone metastases. This success has renewed interest in targeted alpha-particle therapy development for visceral and bone metastasis. This review will discuss (i) the biology of bone metastasis, especially focusing on the vicious cycle of bone metastasis, (ii) how bone remodeling has been exploited to administer systemic radiotherapies, and (iii) targeted radiotherapy development and progress in the development of targeted alpha-particle therapy for the treatment of prostate cancer bone metastasis.
Topics: Alpha Particles; Bone Neoplasms; Humans; Ligands; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiopharmaceuticals
PubMed: 33918705
DOI: 10.3390/molecules26082162