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Medicina (Kaunas, Lithuania) Apr 2024Radioactivity is a process in which the nuclei of unstable atoms spontaneously decay, producing other nuclei and releasing energy in the form of ionizing radiation in... (Review)
Review
Radioactivity is a process in which the nuclei of unstable atoms spontaneously decay, producing other nuclei and releasing energy in the form of ionizing radiation in the form of alpha (α) and beta (β) particles as well as the emission of gamma (γ) electromagnetic waves. People may be exposed to radiation in various forms, as casualties of nuclear accidents, workers in power plants, or while working and using different radiation sources in medicine and health care. Acute radiation syndrome (ARS) occurs in subjects exposed to a very high dose of radiation in a very short period of time. Each form of radiation has a unique pathophysiological effect. Unfortunately, higher organisms-human beings-in the course of evolution have not acquired receptors for the direct "capture" of radiation energy, which is transferred at the level of DNA, cells, tissues, and organs. Radiation in biological systems depends on the amount of absorbed energy and its spatial distribution, particularly depending on the linear energy transfer (LET). Photon radiation with low LET leads to homogeneous energy deposition in the entire tissue volume. On the other hand, radiation with a high LET produces a fast Bragg peak, which generates a low input dose, whereby the penetration depth into the tissue increases with the radiation energy. The consequences are mutations, apoptosis, the development of cancer, and cell death. The most sensitive cells are those that divide intensively-bone marrow cells, digestive tract cells, reproductive cells, and skin cells. The health care system and the public should raise awareness of the consequences of ionizing radiation. Therefore, our aim is to identify the consequences of ARS taking into account radiation damage to the respiratory system, nervous system, hematopoietic system, gastrointestinal tract, and skin.
Topics: Humans; Radiation, Ionizing; Acute Radiation Syndrome; Human Body; Linear Energy Transfer
PubMed: 38674299
DOI: 10.3390/medicina60040653 -
Clinical Cancer Research : An Official... Apr 2021Most patients with prostate cancer treated with androgen receptor (AR) signaling inhibitors develop therapeutic resistance due to restoration of AR functionality. Thus,...
PURPOSE
Most patients with prostate cancer treated with androgen receptor (AR) signaling inhibitors develop therapeutic resistance due to restoration of AR functionality. Thus, there is a critical need for novel treatment approaches. Here we investigate the theranostic potential of hu5A10, a humanized mAb specifically targeting free PSA ().
EXPERIMENTAL DESIGN
LNCaP-AR (LNCaP with overexpression of wildtype AR) xenografts (NSG mice) and _Hi- transgenic mice were imaged with Zr- or treated with Y- or Ac-labeled hu5A10; biodistribution and subcellular localization were analyzed by gamma counting, PET, autoradiography, and microscopy. Therapeutic efficacy of [Ac]hu5A10 and [Y]hu5A10 in LNCaP-AR tumors was assessed by tumor volume measurements, time to nadir (TTN), time to progression (TTP), and survival. Pharmacokinetics of [Zr]hu5A10 in nonhuman primates (NHP) were determined using PET.
RESULTS
Biodistribution of radiolabeled hu5A10 constructs was comparable in different mouse models. Specific tumor uptake increased over time and correlated with PSA expression. Treatment with [Y]/[Ac]hu5A10 effectively reduced tumor burden and prolonged survival ( ≤ 0.0054). Effects of [Y]hu5A10 were more immediate than [Ac]hu5A10 (TTN, < 0.0001) but less sustained (TTP, < 0.0001). Complete responses were observed in 7 of 18 [Ac]hu5A10 and 1 of 9 mice [Y]hu5A10. Pharmacokinetics of [Zr]hu5A10 were consistent between NHPs and comparable with those in mice. [Zr]hu5A10-PET visualized the NHP-prostate over the 2-week observation period.
CONCLUSIONS
We present a complete preclinical evaluation of radiolabeled hu5A10 in mouse prostate cancer models and NHPs, and establish hu5A10 as a new theranostic agent that allows highly specific and effective downstream targeting of AR in PSA-expressing tissue. Our data support the clinical translation of radiolabeled hu5A10 for treating prostate cancer.
Topics: Alpha Particles; Animals; Beta Particles; Disease Models, Animal; Electrons; Linear Energy Transfer; Macaca fascicularis; Male; Mice; Mice, Inbred BALB C; Positron-Emission Tomography; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunotherapy; Receptors, Androgen; Tissue Distribution
PubMed: 33441295
DOI: 10.1158/1078-0432.CCR-20-3614 -
Health Physics May 2021Yttrium-90 (90Y)-polymer composite (RadioGel™) is a new cancer therapeutic agent for treating solid tumors by direct interstitial injection. The 90Y-composite...
Yttrium-90 (90Y)-polymer composite (RadioGel™) is a new cancer therapeutic agent for treating solid tumors by direct interstitial injection. The 90Y-composite comprises insoluble, microscopic yttrium-phosphate particles carried by a sterile, injectable water-polymer (hydrogel) solution that can be placed directly by needle injection into solid tumors. The yttrium-90-RadioGel™ agent was designed to provide a safe, effective, localized, high-dose beta radiation for treating solid tumors. The properties of 90Y-RadioGel™ also make it a relatively safe agent for health care personnel who prepare, handle, and administer the material. The purpose of this work was to demonstrate and characterize radiation safety of the injectable 90Y-RadioGel™ therapeutic agent. Safety in the patient is defined by its ability to target precisely and remain confined within tumor tissue so that radiation doses are imparted to the tumor and not to normal organs and tissues. Radiation safety for health care personnel is defined by the low radiation doses received by persons who prepare and administer the agent. These safety features were demonstrated during experiments, first involving laboratory rabbits and second in cat and dog animal patients that were treated clinically for sarcoma tumors. This paper focuses mainly on the rabbit tissue biodistribution study; follow-on clinical application in cat and dog subjects confirmed the rabbit results. Implanted VX2 liver tumors in the hind limbs of 26 New Zealand White rabbits were treated using tracer amounts of either (a) 90Y-RadioGel™ or (b) 90Y-microparticles in phosphate-buffered saline (PBS) without the gel carrier. Tumor and margin injections were interstitial. Rabbits were euthanized at 48 h or 10 d following injection. Blood and tissues (tumor or tumor margins, liver, lymph nodes, rib bone, kidney, spleen) were collected for liquid scintillation counting using wet-ash procedures. Biodistribution was also analyzed at 10 d post-injection using micro-computed tomography. Thirteen cat and dog subjects were also treated clinically for sarcomas. Liquid scintillation counting at 48 h post-injection of tumors or margins with 90Y-RadioGel™ showed that significant radioactivity was measurable only at the site of administration and that radioactivity above detector background was not found in blood or peripheral organs and tissues. At 10 d post-injection, microCT showed that yttrium phosphate microparticles were confined to the injection site. Yttrium-90 remained where placed and did not migrate away in significant amounts from the injection site. Radiation doses were confined mainly to tumors and margin tissues. During preparation and administration, radiation doses to hands and body of study personnel were negligible. This work showed that 90Y-RadioGel™ can be safely prepared and administered and that radiation doses to cancer patients are confined to tumor and margin tissues rather than to critical normal organs and tissues.
Topics: Animals; Cats; Dogs; Neoplasms; Polymers; Rabbits; Radioimmunotherapy; Tissue Distribution; X-Ray Microtomography; Yttrium Radioisotopes
PubMed: 33760767
DOI: 10.1097/HP.0000000000001369 -
Frontiers in Pharmacology 2019Glioblastoma is the most common malignant adult brain tumor and has a very poor patient prognosis. The mean survival for highly proliferative glioblastoma is only 10 to... (Review)
Review
Glioblastoma is the most common malignant adult brain tumor and has a very poor patient prognosis. The mean survival for highly proliferative glioblastoma is only 10 to 14 months despite an aggressive current therapeutic approach known as Stupp's protocol, which consists of debulking surgery followed by radiotherapy and chemotherapy. Despite several clinical trials using anti-angiogenic targeted therapies, glioblastoma medical care remains without major progress in the last decade. Recent progress in nuclear medicine, has been mainly driven by advances in biotechnologies such as radioimmunotherapy, radiopeptide therapy, and radionanoparticles, and these bring a new promising arsenal for glioblastoma therapy. For therapeutic purposes, nuclear medicine practitioners classically use β particle emitters like I, Y, Re, or Lu. In the glioblastoma field, these radioisotopes are coupled with nanoparticles, monoclonal antibodies, or peptides. These radiopharmaceutical compounds have resulted in a stabilization and/or improvement of the neurological status with only transient side effects. In nuclear medicine, the glioblastoma-localized and targeted internal radiotherapy proof-of-concept stage has been successfully demonstrated using β emitting isotopes. Similarly, α particle emitters like Bi, At, or Ac appear to be an innovative and interesting alternative. Indeed, α particles deliver a high proportion of their energy inside or at close proximity to the targeted cells (within a few micrometers from the emission point versus several millimeters for β particles). This physical property is based on particle-matter interaction differences and results in α particles being highly efficient in killing tumor cells with minimal irradiation of healthy tissues and permits targeting of isolated tumor cells. The first clinical trials confirmed this idea and showed good therapeutic efficacy and less side effects, thus opening a new and promising era for glioblastoma medical care using α therapy. The objective of this literature review is focused on the developing field of nuclear medicine and aims to describe the various parameters such as targets, vectors, isotopes, or injection route (systemic and local) in relation to the clinical and preclinical results in glioblastoma pathology.
PubMed: 31354487
DOI: 10.3389/fphar.2019.00772 -
Nuclear Medicine Review. Central &... Aug 2012Iodine-131 is successfully used in the treatment of hyperthyroidism and differentiated thyroid cancer. Thyroid is the critical organ for iodine. Iodine is taken up by... (Review)
Review
Iodine-131 is successfully used in the treatment of hyperthyroidism and differentiated thyroid cancer. Thyroid is the critical organ for iodine. Iodine is taken up by the thyroid follicular cells. Radioactive isotope iodine-131 simultaneously emits two types of radiation: radiation beta minus (β-) used for the treatment and gamma (γ) used for diagnosis. Due to the penetration of beta particles in tissue, damaging effect of β-radiation is restricted to thyroid cells. In this article, characteristic of iodine-131, mechanism of action and mechanism of tissue damage is presented. HIGH energy γ-ray emission, contributes to the dose of both: patient's body and the personnel. In accordance with the principles of radiation protection, reducing exposure to ionizing radiation should be achieved by: use of proper shieldings, organization of work, appropriate distance from the radiation source and reducing the time of exposure. Treatment with I-131, depending on medical indications, may be carried out on stationary or outpatient basis. All activities conducted in the exposure to radiation must comply with the principles of radiation protection, in accordance with the applicable regulations, that are also presented in this article.
Topics: Humans; Iodine Radioisotopes; Physical Phenomena; Practice Guidelines as Topic; Radiobiology; Safety; Thyroid Diseases
PubMed: 22936505
DOI: No ID Found -
Journal of Labelled Compounds &... Jul 2018Radiometals are becoming increasingly accessible and are utilized frequently in the design of radiotracers for imaging and therapy. Nuclear properties ranging from the... (Review)
Review
Radiometals are becoming increasingly accessible and are utilized frequently in the design of radiotracers for imaging and therapy. Nuclear properties ranging from the emission of γ-rays and β -particles (imaging) to Auger electron and β and α-particles (therapy) in combination with long half-lives are ideally matched with the relatively long biological half-life of monoclonal antibodies in vivo. Radiometal labeling of antibodies requires the incorporation of a metal chelate onto the monoclonal antibody. This chelate must coordinate the metal under mild conditions required for the handling of antibodies, as well as provide high kinetic, thermodynamic, and metabolic stability once the metal ion is coordinated to prevent release of the radionuclide before the target site is reached in vivo. Herein, we review the role of different radiometals that have found applications of the design of radiolabeled antibodies for imaging and radioimmunotherapy. Each radionuclide is described regarding its nuclear synthesis, coordinative preference, and radiolabeling properties with commonly used and novel chelates, as well as examples of their preclinical and clinical applications. An overview of recent trends in antibody-based radiopharmaceuticals is provided to spur continued development of the chemistry and application of radiometals for imaging and therapy.
Topics: Animals; Antibodies; Chelating Agents; Chemistry Techniques, Synthetic; Humans; Isotope Labeling; Metals; Radioactive Tracers
PubMed: 29230857
DOI: 10.1002/jlcr.3590 -
The Quarterly Journal of Nuclear... Dec 2021The concept of theragnostics goes back to the earliest days of nuclear medicine, with [I/I]iodide in thyroid disease and [I/I]MIBG in phaeochromocytoma being examples in...
The concept of theragnostics goes back to the earliest days of nuclear medicine, with [I/I]iodide in thyroid disease and [I/I]MIBG in phaeochromocytoma being examples in long-term use. However, in recent years there has been a great expansion in the application of theragnostics, beginning with [Ga/Lu]-labelled somatostatin peptides for evaluation and treatment of neuroendocrine tumors. We are currently seeing the rapid development of [Ga/Lu]PSMA theragnostics in metastatic prostate cancer. While these applications are very promising, there are a number of practicalities which must be addressed in the development and introduction of novel theragnostics. The physical half-lives of the diagnostic and therapeutic radionuclides must be appropriate for imaging and delivery of targeted cell killing, respectively. The types of radioactive emissions are critical; beta particles can traverse several millimeters but also risk damaging non-target tissues, while alpha particles deliver their energy over a much shorter path length, a few cell diameters, and must be more directly targeted. It must be practical to produce the therapeutic radionuclide and the final radiopharmaceutical and deliver them to the final user within an appropriate time-frame determined by half-life and stability. The biodistribution of the agent must demonstrate adequate accumulation and retention in the target tissue with clearance from adjacent and/or radio-sensitive normal tissues. The commercial success of recently introduced theragnostics suggests a rosy future for personalized medicine.
Topics: Humans; Male; Nuclear Medicine; Prostatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Tissue Distribution
PubMed: 34881851
DOI: 10.23736/S1824-4785.21.03424-5 -
International Journal of Molecular... Jul 2015In the following study, dose dependent effects on growth and oxidative stress induced by β-radiation were examined to gain better insights in the mode of action of...
In the following study, dose dependent effects on growth and oxidative stress induced by β-radiation were examined to gain better insights in the mode of action of β-radiation induced stress in plant species. Radiostrontium (⁹⁰Sr) was used to test for β-radiation induced responses in the freshwater macrophyte Lemna minor. The accumulation pattern of 90Sr was examined for L. minor root and fronds separately over a seven-day time period and was subsequently used in a dynamic dosimetric model to calculate β-radiation dose rates. Exposing L. minor plants for seven days to a ⁹⁰Sr activity concentration of 25 up to 25,000 kBq·L⁻¹ resulted in a dose rate between 0.084 ± 0.004 and 97 ± 8 mGy·h⁻¹. After seven days of exposure, root fresh weight showed a dose dependent decrease starting from a dose rate of 9.4 ± 0.5 mGy·h⁻¹. Based on these data, an EDR10 value of 1.5 ± 0.4 mGy·h⁻¹ was estimated for root fresh weight and 52 ± 17 mGy·h⁻¹ for frond fresh weight. Different antioxidative enzymes and metabolites were further examined to analyze if β-radiation induces oxidative stress in L. minor.
Topics: Antioxidants; Araceae; Beta Particles; Metabolome; Radiometry; Stress, Physiological; Strontium Radioisotopes; Time Factors
PubMed: 26198226
DOI: 10.3390/ijms160715309 -
Sensors (Basel, Switzerland) Dec 2022In order to detect special nuclear materials and other radioactive materials in Security and Defense scenarios, normally, a combination of neutron and gamma-ray...
In order to detect special nuclear materials and other radioactive materials in Security and Defense scenarios, normally, a combination of neutron and gamma-ray detection systems is used. In particular, to avoid illicit traffic of special nuclear materials and radioactive sources/materials, radiation portal monitors are placed at seaports to inspect shipping-container cargo. Despite their large volume (high efficiency), these detection systems are expensive, and therefore only a fraction of these containers are inspected. In this work, a novel mobile radiation detection system is presented, based on an EJ-200 plastic scintillator for the detection of gamma rays and beta particles, and a neutron detector EJ-426HD plastic scintillator (with Li) embedded in a compact and modular moderator. The use of silicon photomultipliers in both detectors presented advantages such as lightweight, compactness, and low power consumption. The developed detection system was integrated in a highly maneuverable multirotor. Monte Carlo simulations were validated by laboratory measurements and field tests were performed using real gamma-ray and neutron sources. The detection and localization within one meter was achieved using a maximum likelihood estimation algorithm for Cs sources (4 MBq), as well as the detection of Am-beryllium (1.45 GBq) source placed inside the shipping container.
Topics: Scintillation Counting; Gamma Rays; Neutrons; Radiation Monitoring; Plastics
PubMed: 36616926
DOI: 10.3390/s23010329 -
Tumour Biology : the Journal of the... Jun 2012The effectiveness of targeted α-therapy (TAT) can be explained by the properties of α-particles. Alpha particles are helium nuclei and are ~8,000 times larger than... (Review)
Review
The effectiveness of targeted α-therapy (TAT) can be explained by the properties of α-particles. Alpha particles are helium nuclei and are ~8,000 times larger than β(-)-particles (electrons). When emitted from radionuclides that decay via an α-decay pathway, they release enormous amounts of energy over a very short distance. Typically, the range of α-particles in tissue is 50-100 μm and they have high linear energy transfer (LET) with a mean energy deposition of 100 keV/μm, providing a more specific tumor cell killing ability without damage to the surrounding normal tissues than β(-)-emitters. Due to these properties, the majority of pre-clinical and clinical trials have demonstrated that α-emitters such as (225)Ac, (211)At, (212)Bi, (213)Bi, (212)Pb, (223)Ra, and (227)Th are ideal for the treatment of smaller tumor burdens, micrometastatic disease, and disseminated disease. Even though these α-emitters have favorable properties, the development of TAT has been limited by high costs, unresolved chemistry, and limited availability of the radionuclides. To overcome these limitations, more potent isotopes, additional sources, and more efficient isotope production methods should be addressed. Furthermore, better chelation and labeling methods with the improvements of isotope delivery, targeting vehicles, molecular targets, and identification of appropriate clinical applications are still required.
Topics: Alpha Particles; Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Neoplasms; Radioimmunotherapy; Radioisotopes
PubMed: 22143940
DOI: 10.1007/s13277-011-0286-y