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The Tohoku Journal of Experimental... Apr 2009Radiopharmaceuticals are used in nuclear medicine for diagnostic and therapeutic purposes. Many adverse reactions and false positive reactions related to... (Review)
Review
Radiopharmaceuticals are used in nuclear medicine for diagnostic and therapeutic purposes. Many adverse reactions and false positive reactions related to radiopharmaceuticals take place every day in hospitals, but most of them are not reported. It is therefore important to understand the definition of each undesirable reaction. Adverse reactions are defined as any noxious or unintended reactions to a drug, which is administered in standard doses through the proper route for the purpose of prophylaxis, diagnosis, or treatment. False positive reactions can be defined as any imaging appearance caused by undue physiological or pathological accumulation of radiopharmaceuticals. Information concerning these undesirable reactions is limited for radiopharmaceuticals. The present study intends to be a source of information that could be accessed by all nuclear medicine staff. A review of the literature from 1957 to January 2009 was carried out using the criteria of a systematic review, established by the Cochrane Collaboration, an international non-profit organization, that provides up-to-date information about the health care. The present study has revealed that radiopharmaceuticals cause adverse reactions. Six cases of adverse reactions with radiopharmaceuticals were found: 2 cases with (18)F-fluorodeoxyglucose (FDG) and 4 cases with technetium 99m ((99m)Tc). Among the 4 cases of adverse reactions with (99m)Tc, one subject who received (99m)Tc-labeled sestamibi developed anaphylactic reactions. Moreover, a total of 8 cases with false positive reactions were found with FDG. In conclusion, a worldwide effort should be made to report as many cases as possible of adverse events and false positive reactions with radiopharmaceuticals.
Topics: False Positive Reactions; Fluorodeoxyglucose F18; Humans; Nuclear Medicine; Radiopharmaceuticals; Technetium
PubMed: 19346729
DOI: 10.1620/tjem.217.251 -
International Journal of Molecular... Jan 2023Tc is one of the predominant fission products of U and an important component of nuclear industry wastes. The long half-life and specific activity of Tc (212,000 y, 0.63...
New Preparative Approach to Purer Technetium-99 Samples-Tetramethylammonium Pertechnetate: Deep Understanding and Application of Crystal Structure, Solubility, and Its Conversion to Technetium Zero Valent Matrix.
Tc is one of the predominant fission products of U and an important component of nuclear industry wastes. The long half-life and specific activity of Tc (212,000 y, 0.63 GBq g) makes Tc a hazardous material. Two principal ways were proposed for its disposal, namely, long-term storage and transmutation. Conversion to metal-like technetium matrices is highly desirable for both cases and for the second one the reasonably high Tc purity was important too. Tetramethylammonium pertechnetate (TMAP) was proposed here as a prospective precursor for matrix manufacture. It provided with very high decontamination factors from actinides (that is imperative for transmutation) by means of recrystallisation and it was based on the precise data on TMAP solubility and thermodynamics accomplished in the temperature range of 3-68 °C. The structure of solid pertechnetates were re-estimated with precise X-ray structure solution and compared to its Re and Cl analogues and tetrabutylammonium analogue as well. Differential thermal and evolved gas analysis in a flow of Ar-5% H gas mixture showed that the major products of thermolysis were pure metallic technetium in solid matrix, trimethylammonium, carbon dioxide, and water in gas phase. High decontamination factors have been achieved when TMAP was used as an intermediate precursor for Tc.
Topics: Technetium; Sodium Pertechnetate Tc 99m; Solubility; Prospective Studies
PubMed: 36768335
DOI: 10.3390/ijms24032015 -
Journal of Medicinal Chemistry Apr 2023Technetium-99m is the workhorse of diagnostic nuclear medicine. The aim of the work is to analyze the technetium-99m patents since 2000 to photograph its innovation.... (Review)
Review
Technetium-99m is the workhorse of diagnostic nuclear medicine. The aim of the work is to analyze the technetium-99m patents since 2000 to photograph its innovation. QUESTEL's ORBIT Intelligence system was used for the collection of technetium inventions disclosed in patents and patent applications in more than 96 countries in the period 2000-2022; 2768 patent documents were analyzed. Patent counting and analysis have shown that SPECT imaging using technetium-99m radiopharmaceuticals is still robust. The introduction of new technetium-99m radiopharmaceuticals into clinical routine goes beyond successful trials. In eastern economies, such as China and other emerging markets, patent applications are on the rise, while those in developed western countries are stagnating, with some exceptions for the United States. But despite the difficulties, academic and industrial research on these tracers remains essential for the development of nuclear medicine.
Topics: United States; Technetium; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; China
PubMed: 37010457
DOI: 10.1021/acs.jmedchem.3c00148 -
Journal of Nuclear Medicine : Official... May 1975Exogenous fibrinogen has been successfully labeled with 99mTc using a modified electrolytic method. The exact labeling mechanism has not been determined. Experimental...
Exogenous fibrinogen has been successfully labeled with 99mTc using a modified electrolytic method. The exact labeling mechanism has not been determined. Experimental data suggest that the labeling process of 99mTc-fibrinogen is quite similar to that of 99mTc-human serum albumin as reported earlier by Benjamin. Technetium-99m-fibrinogen is stable in human plasma or in 1% buffered human serum albumin. A binding efficiency of 76% has been achieved with approximately 25% clottable protein. The entire labeling procedure requires less than 1 hr of preparation time. This short labeling time in a closed system may allow development of a practical method for labeling autologous fibrinogen, thus eliminating the risk of hepatitis transmission.
Topics: Fibrinogen; Humans; Isotope Labeling; Technetium
PubMed: 1194984
DOI: No ID Found -
PloS One 2023Infectious diseases caused by bacteria that have become resistant to antibiotics have increased in prevalence, necessitating new methods for their diagnosis and...
Infectious diseases caused by bacteria that have become resistant to antibiotics have increased in prevalence, necessitating new methods for their diagnosis and treatment. The aim of this study was to compare the efficacy of synthetic ciprofloxacin to that of organic ciprofloxacin produced by cave microorganisms, as well as to evaluate the feasibility of using organic ciprofloxacin radiolabeled with technetium-99m as an imaging agent. Organic ciprofloxacin produced by cave bacteria isolated from sediment taken from the dark zone of Antalya's "Yark Sinkhole," (Turkey's 14th deepest cave), was purified using high-performance liquid chromatography. Purified organic ciprofloxacin and standard ciprofloxacin were radiolabeled with technetium-99m (99mTc), and their uptake by pathogenic microorganisms as well as potential as an imaging agent were examined. According to thin-layer radiochromatography, radiolabeling efficiencies were 98.99 ± 0.34 (n = 7) and 91.25 ± 1.84 (n = 7) for radiolabeled organic ciprofloxacin and standard ciprofloxacin respectively. The binding efficiency of radiolabeled organic ciprofloxacin at the 240th minute was higher compared with radiolabeled standard ciprofloxacin, especially with P.aeruginosa, MRSA, VRE and E.coli. The results demonstrate that radiolabeling with 99mTc does not alter the biological behavior of organic ciprofloxacin, and radiolabeled organic ciprofloxacin has potential as an imaging agent for the detection of bacterial infection. The original value of the study is the monitoring of the antibiofilm effects of untouched cave-derived organic antibiotics by radiolabeling with a radionuclide.
Topics: Ciprofloxacin; Technetium; Radiopharmaceuticals; Radionuclide Imaging; Anti-Bacterial Agents; Escherichia coli
PubMed: 37943851
DOI: 10.1371/journal.pone.0291342 -
Journal of Nuclear Medicine : Official... Jun 1968
Topics: Iodine Isotopes; Methods; Photography; Radioisotopes; Radionuclide Imaging; Technetium; Xenon
PubMed: 5647700
DOI: No ID Found -
Molecular Imaging and Biology Jun 2022Dysregulated activity of matrix metalloproteinases (MMPs) drives a variety of pathophysiological conditions. Non-invasive imaging of MMP activity in vivo promises...
INTRODUCTION
Dysregulated activity of matrix metalloproteinases (MMPs) drives a variety of pathophysiological conditions. Non-invasive imaging of MMP activity in vivo promises diagnostic and prognostic value. However, current targeting strategies by small molecules are typically limited with respect to the bioavailability of the labeled MMP binders in vivo. To this end, we here introduce and compare three chemical modifications of a recently developed barbiturate-based radiotracer with respect to bioavailability and potential to image MMP activity in vivo.
METHODS
Barbiturate-based MMP inhibitors with an identical targeting unit but varying hydrophilicity were synthesized, labeled with technetium-99m, and evaluated in vitro and in vivo. Biodistribution and radiotracer elimination were determined in C57/BL6 mice by serial SPECT imaging. MMP activity was imaged in a MMP-positive subcutaneous xenograft model of human K1 papillary thyroid tumors. In vivo data were validated by scintillation counting, autoradiography, and MMP immunohistochemistry.
RESULTS
We prepared three new Tc-labeled MMP inhibitors, bearing either a glycine ([Tc]MEA39), lysine ([Tc]MEA61), or the ligand HYNIC with the ionic co-ligand TPPTS ([Tc]MEA223) yielding gradually increasing hydrophilicity. [Tc]MEA39 and [Tc]MEA61 were rapidly eliminated via hepatobiliary pathways. In contrast, [Tc]MEA223 showed delayed in vivo clearance and primary renal elimination. In a thyroid tumor xenograft model, only [Tc]MEA223 exhibited a high tumor-to-blood ratio that could easily be delineated in SPECT images.
CONCLUSION
Introduction of HYNIC/TPPTS into the barbiturate lead structure ([Tc]MEA223) results in delayed renal elimination and allows non-invasive MMP imaging with high signal-to-noise ratios in a papillary thyroid tumor xenograft model.
Topics: Animals; Barbiturates; Biological Availability; Humans; Ligands; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Mice; Technetium; Thyroid Neoplasms; Tissue Distribution; Tomography, Emission-Computed, Single-Photon
PubMed: 34750717
DOI: 10.1007/s11307-021-01668-z -
Inorganic Chemistry Dec 2023The discovery and development of new Tc-based radiopharmaceuticals or labeled drugs in general is based on innovative, pure chemistry and subsequent,...
The discovery and development of new Tc-based radiopharmaceuticals or labeled drugs in general is based on innovative, pure chemistry and subsequent, application-targeted research. This was the case for all currently clinically applied imaging agents. Most of them were market-introduced some 20 years ago, and the few more recent ones are based on even older chemistry, albeit technetium chemistry has made substantial progress over the last 20 years. This progress though is not mirrored by new molecular imaging agents and is even accompanied by a steady decrease in the number of groups active in pure and applied technetium chemistry, a contrast to the trends in most other fields in which d-elements play a central role. The decrease in research with technetium has been partly counterbalanced by a strong increase of research activities with homologous, cold rhenium compounds for therapy, disclosing in the future eventually a quite unique opportunity for theranostics. This Viewpoint analyzes the pathways that led to radiopharmaceuticals in the past and their underlying fundamental contributions. It attempts to tackle the question of why new chemistry still does not lead to new imaging agents, i.e., the question of whether pure technetium chemistry is still needed at all.
Topics: Technetium; Radiopharmaceuticals; Molecular Imaging; Rhenium
PubMed: 37417737
DOI: 10.1021/acs.inorgchem.3c01620 -
Clinical Medicine (London, England) Oct 2017Molecular radiotheragnostics directly links nuclear medicine diagnostic imaging to therapy. The imaging study is used to detect a specific molecular target associated...
Molecular radiotheragnostics directly links nuclear medicine diagnostic imaging to therapy. The imaging study is used to detect a specific molecular target associated with a disease process. A radiotherapeutic molecule with a similar biodistribution to the diagnostic agent can then be used to deliver targeted therapy.Molecular radiotheragnostics have been applied to manage both benign and malignant thyroid disease since the 1940s. The specific molecular pathway targeted is the sodium/iodide symporter (NIS) located on the basolateral membrane of the thyroid follicular cell. Radiolabelling of iodide or a similar ion allows targeting of the NIS system with radiopharmaceuticals for imaging (I-radioiodine and Tc-pertechnetate) and treatment (I-radioiodine) by virtue of their gamma ray and beta-particle emissions, respectively.Scintigraphic imaging directly guides I-radioiodine treatment planning to maximise therapeutic benefit while minimising adverse reactions, in a personalised medicine approach.
Topics: Humans; Iodine Radioisotopes; Pathology, Molecular; Radionuclide Imaging; Radiopharmaceuticals; Radiotherapy; Symporters; Technetium; Thyroid Diseases; Thyroid Gland
PubMed: 28974598
DOI: 10.7861/clinmedicine.17-5-453 -
International Journal of Molecular... Dec 2021Auger electron-emitters increasingly attract attention as potential radionuclides for molecular radionuclide therapy in oncology. The radionuclide technetium-99m is...
Auger electron-emitters increasingly attract attention as potential radionuclides for molecular radionuclide therapy in oncology. The radionuclide technetium-99m is widely used for imaging; however, its potential as a therapeutic radionuclide has not yet been fully assessed. We used MDA-MB-231 breast cancer cells engineered to express the human sodium iodide symporter-green fluorescent protein fusion reporter (hNIS-GFP; MDA-MB-231.hNIS-GFP) as a model for controlled cellular radionuclide uptake. Uptake, efflux, and subcellular location of the NIS radiotracer [Tc]TcO were characterised to calculate the nuclear-absorbed dose using Medical Internal Radiation Dose formalism. Radiotoxicity was determined using clonogenic and γ-H2AX assays. The daughter radionuclide technetium-99 or external beam irradiation therapy (EBRT) served as controls. [Tc]TcO in vivo biodistribution in MDA-MB-231.hNIS-GFP tumour-bearing mice was determined by imaging and complemented by ex vivo tissue radioactivity analysis. [Tc]TcO resulted in substantial DNA damage and reduction in the survival fraction (SF) following 24 h incubation in hNIS-expressing cells only. We found that 24,430 decays/cell (30 mBq/cell) were required to achieve SF (95%-confidence interval = [SF; SF]). Different approaches for determining the subcellular localisation of [Tc]TcO led to SF nuclear-absorbed doses ranging from 0.33 to 11.7 Gy. In comparison, EBRT of MDA-MB-231.hNIS-GFP cells resulted in an SF of 2.59 Gy. In vivo retention of [Tc]TcO after 24 h remained high at 28.0% ± 4.5% of the administered activity/gram tissue in MDA-MB-231.hNIS-GFP tumours. [Tc]TcO caused DNA damage and reduced clonogenicity in this model, but only when the radioisotope was taken up into the cells. This data guides the safe use of technetium-99m during imaging and potential future therapeutic applications.
Topics: Breast Neoplasms; Cell Line, Tumor; Dose-Response Relationship, Radiation; Humans; Iodine Radioisotopes; Radiopharmaceuticals; Symporters; Technetium; Tissue Distribution
PubMed: 34948266
DOI: 10.3390/ijms222413466