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Frontiers in Pharmacology 2018The last decade has seen rapid growth in the use of theranostic radionuclides for the treatment and imaging of a wide range of cancers. Radionuclide therapy and imaging... (Review)
Review
The last decade has seen rapid growth in the use of theranostic radionuclides for the treatment and imaging of a wide range of cancers. Radionuclide therapy and imaging rely on a radiolabeled vector to specifically target cancer cells. Radionuclides that emit β particles have thus far dominated the field of targeted radionuclide therapy (TRT), mainly because the longer range (μm-mm track length) of these particles offsets the heterogeneous expression of the molecular target. Shorter range (nm-μm track length) α- and Auger electron (AE)-emitting radionuclides on the other hand provide high ionization densities at the site of decay which could overcome much of the toxicity associated with β-emitters. Given that there is a growing body of evidence that other sensitive sites besides the DNA, such as the cell membrane and mitochondria, could be critical targets in TRT, improved techniques in detecting the subcellular distribution of these radionuclides are necessary, especially since many β-emitting radionuclides also emit AE. The successful development of TRT agents capable of homing to targets with subcellular precision demands the parallel development of quantitative assays for evaluation of spatial distribution of radionuclides in the nm-μm range. In this review, the status of research directed at subcellular targeting of radionuclide theranostics and the methods for imaging and quantification of radionuclide localization at the nanoscale are described.
PubMed: 30233374
DOI: 10.3389/fphar.2018.00996 -
World Journal of Nuclear Medicine 2015Radiosynovectomy is a well-established therapy in arthritis and involves an intra-articular injection of small radioactive particles to treat a synovitis. In Europe,... (Review)
Review
Radiosynovectomy is a well-established therapy in arthritis and involves an intra-articular injection of small radioactive particles to treat a synovitis. In Europe, frequent indications are rheumatoid and poly-arthritis. Especially in Germany radiosynovectomy is the second common therapy in Nuclear Medicine with about 40,000-60,000 treated joints per year. In Spain, USA, Turkey, Argentines and Philippines the therapy is more use in hemophilic arthritis with excellent results. Especially in developing countries with low availability of clotting factors, the radiosynovectomy represent a cost effective therapeutic option for repeated bleedings in hemophilic arthropathy. The special focus in these countries is maintaining of mobility and work ability. Often only the knee and medium joints (ankle, elbow and shoulder) are treated using yttrium-90, rhenium-186 or phosphorus-32. However, in rheumatoid arthritis most common affected joints are the fingers. For the treatment in these small joints, erbium-169 is necessary. Unfortunately, erbium-169 is only available in Europe. Further indications for radiosynovectomy are osteoarthritis and the articular effusion after joint replacement. The reported response rates in rheumatoid and poly-arthritis range from 60% to 80% depends from the stage of previous arthrosis. The best effectiveness of therapy was observed in hemophilic arthritis with response rate of 90% and significant reducing of bleeding frequency. The therapy is well-tolerated with low rate of side effects. In respect of the specific uptake of particles in the synovia and short range of beta radiation, the radiation exposure outside the joint is very low. The radiosynovectomy has efforts in comparison to surgical synovectomy: it's a minor intervention with low costs; and simultaneous treatments of multiple joints or treatment in short intervals are possible. The presented paper summarized the published papers and reports our own experiences in >15,000 treated joints.
PubMed: 25709538
DOI: 10.4103/1450-1147.150509 -
The Quarterly Journal of Nuclear... Dec 2004An important consideration in the development of effective strategies for radioimmunotherapy is the nature of the radiation emitted by the radionuclide. Radionuclides... (Review)
Review
An important consideration in the development of effective strategies for radioimmunotherapy is the nature of the radiation emitted by the radionuclide. Radionuclides decaying by the emission of alpha-particles offer the possibility of matching the cell specific reactivity of monoclonal antibodies with radiation with a range of only a few cell diameters. Furthermore, alpha-particles have important biological advantages compared with external beam radiation and beta-particles including a higher biological effectiveness, which is nearly independent of oxygen concentration, dose rate and cell cycle position. In this review, the clinical settings most likely to benefit from alpha-particle radioimmunotherapy will be discussed. The current status of preclinical and clinical research with antibodies labeled with 3 promising alpha-particle emitting radionuclides - (213)Bi, (225)Ac, and (211)At - also will be summarized.
Topics: Actinium; Alpha Particles; Antibodies, Monoclonal; Astatine; Bismuth; Humans; Isotopes; Neoplasms; Practice Patterns, Physicians'; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals; Treatment Outcome
PubMed: 15640792
DOI: No ID Found -
Molecules (Basel, Switzerland) Aug 2022Advances in the field of molecular biology have had an impact on biomedical applications, which provide greater hope for both imaging and therapeutics. Work has been... (Review)
Review
Advances in the field of molecular biology have had an impact on biomedical applications, which provide greater hope for both imaging and therapeutics. Work has been intensified on the development of radionuclides and their application in radiopharmaceuticals (RP) which will certainly influence and expand therapeutic approaches in the future treatment of patients. Alpha or beta particles and Auger electrons are used for therapy purposes, and each has advantages and disadvantages. The radionuclides labeled drug delivery system will deliver the particles to the specific targeting cell. Different radioligands can be chosen to uniquely target molecular receptors or intracellular components, making them suitable for personal patient-tailored therapy in modern cancer therapy management. Advances in nanotechnology have enabled nanoparticle drug delivery systems that can allow for specific multivalent attachment of targeted molecules of antibodies, peptides, or ligands to the surface of nanoparticles for therapy and imaging purposes. This review presents fundamental radionuclide properties with particular reference to tumor biology and receptor characteristic of radiopharmaceutical targeted therapy development.
Topics: Beta Particles; Diagnostic Imaging; Humans; Neoplasms; Radioisotopes; Radiopharmaceuticals
PubMed: 36014472
DOI: 10.3390/molecules27165231 -
Pathogens (Basel, Switzerland) Feb 2022The handling of highly pathogenic viruses, whether for diagnostic or research purposes, often requires an inactivation step. This article reviews available inactivation... (Review)
Review
The handling of highly pathogenic viruses, whether for diagnostic or research purposes, often requires an inactivation step. This article reviews available inactivation techniques published in peer-reviewed journals and their benefits and limitations in relation to the intended application. The bulk of highly pathogenic viruses are represented by enveloped RNA viruses belonging to the , , , , , , , and families. Here, we summarize inactivation methods for these virus families that allow for subsequent molecular and serological analysis or vaccine development. The techniques identified here include: treatment with guanidium-based chaotropic salts, heat inactivation, photoactive compounds such as psoralens or 1.5-iodonaphtyl azide, detergents, fixing with aldehydes, UV-radiation, gamma irradiation, aromatic disulfides, beta-propiolacton and hydrogen peroxide. The combination of simple techniques such as heat or UV-radiation and detergents such as Tween-20, Triton X-100 or Sodium dodecyl sulfate are often sufficient for virus inactivation, but the efficiency may be affected by influencing factors including quantity of infectious particles, matrix constitution, pH, salt- and protein content. Residual infectivity of the inactivated virus could have disastrous consequences for both laboratory/healthcare personnel and patients. Therefore, the development of inactivation protocols requires careful considerations which we review here.
PubMed: 35215213
DOI: 10.3390/pathogens11020271 -
Journal of Biomedical Optics Feb 2013Cerenkov luminescence imaging is an emerging optical preclinical modality based on the detection of Cerenkov radiation induced by beta particles when traveling though...
Cerenkov luminescence imaging is an emerging optical preclinical modality based on the detection of Cerenkov radiation induced by beta particles when traveling though biological tissues with a velocity greater than the speed of light. We present the first human Cerenkography obtained by detecting Cerenkov radiation escaping the thyroid gland of a patient treated for hyperthyroidism. The Cerenkov light was detected using an electron multiplied charge coupled device and a conventional C-mount lens. The system set-up has been tested by using a slab of ex vivo tissue equal to a 1 cm slice of chicken breast in order to simulate optical photons attenuation. We then imaged for 2 min the head and neck region of a patient treated orally 24 h before with 550 MBq of I-131. Co-registration between photographic and Cerenkov images showed a good localization of the Cerenkov light within the thyroid region. In conclusion, we showed that it is possible to obtain a planar image of Cerenkov photons escaping from a human tissue. Cerenkography is a potential novel medical tool to image superficial organs of patients treated with beta minus radiopharmaceuticals and can be extended to the imaging of beta plus emitters.
Topics: Animals; Beta Particles; Chickens; Diagnostic Imaging; Fluorodeoxyglucose F18; Humans; Hyperthyroidism; Luminescence; Optical Devices; Optical Phenomena; Phantoms, Imaging; Radionuclide Imaging; Radiopharmaceuticals; Radiotherapy Dosage; Thyroid Gland
PubMed: 23334715
DOI: 10.1117/1.JBO.18.2.020502 -
Journal of Radiation Research Aug 2022Internal radiation exposure from neutron-induced radioisotopes that were environmentally activated following an atomic bombing or nuclear accident should be considered... (Review)
Review
Internal radiation exposure from neutron-induced radioisotopes that were environmentally activated following an atomic bombing or nuclear accident should be considered for a complete picture of the pathologic effects on survivors. Inhaled hot particles expose neighboring tissues to very high doses of particle beams, which can cause local tissue damage. Experimentally, a few μm of 55MnO2 powder was irradiated with neutrons at a nuclear reactor in order to generate 56MnO2 that emits β-rays. Rats were irradiated via inhalation. Pathological changes in various rat tissues were examined. In addition, the 56Mn β energy spectrum around the particles was calculated to determine the local dose rate and the cumulative dose. This review focuses on our latest pathological findings in lungs with internal radiation injury and discusses the pathological changes of early event damage caused by localized, very high-dose internal radiation exposure, including apoptosis, elastin stigma, emphysema, hemorrhage and severe inflammation. The pathological findings of lung tissue due to internal radiation exposure of 0.1 Gy were severe, with no pathological changes observed due to external exposure to γ radiation at a dose of 2.0 Gy. Therefore, it is suggested that new pathological analysis methods for internal exposure due to radioactive microparticles are required.
Topics: Animals; Beta Particles; Gamma Rays; Neutrons; Radioactivity; Radioisotopes; Rats
PubMed: 35968993
DOI: 10.1093/jrr/rrac045 -
Journal of Cancer Research and... 2022Most studies suggest that dose-specific radiation regimens are essential for optimal induction of cancer cell response. This study focused on determining...
OBJECTIVE
Most studies suggest that dose-specific radiation regimens are essential for optimal induction of cancer cell response. This study focused on determining β-radiation-absorbed dose (rad) effects on the cell viability, cytotoxicity, hypersensitivity, and cell death of K562 cells using experimental methods and Monte Carlo simulation (MCS).
MATERIALS AND METHODS
The K562 cells were cultured and irradiated with β-particles emitted from a strontium source in vitro, with the estimated daily activity of 1.238 μCi. The treated cells were radiated at least three times every day for 3 consecutive days. The cell viability and apoptosis were investigated in treated cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, DNA electrophoresis, Hoechst dye, and inverted microscope. The average absorbed doses were obtained by MCS (MCNPX code). To verify simulation and experimental results, we used a Geiger-Muller counter and estimated a scaling factor.
RESULTS
The cytotoxic effects and cell death were induced in the treated groups via rad in a time-dependent manner. The highest apoptotic and cytotoxic effects were observed in cells after irradiation with β-particles for 120 min per day in 3 consecutive days. rads were determined using MCNPX code and cell survival rates were significantly reduced during irradiation periods. No significant hyper-radiosensitivity was found based on experimental and theoretical results.
CONCLUSION
Despite the difficult calculation of the rad in the target cells and the scant information in this field, fortunately we have achieved significant theoretical data consistent with the experimental results. Our findings also introduced MCS as a better choice for evaluating of rad effects under different cellular conditions with high accuracy.
Topics: Computer Simulation; Humans; K562 Cells; Monte Carlo Method; Radiation Dosage; Radiometry; Strontium Radioisotopes
PubMed: 35381784
DOI: 10.4103/jcrt.JCRT_909_20