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Seminars in Nuclear Medicine May 2022After introduction of the first commercial combined PET and/or CT technology in 2001, this diagnostic tool quickly became a clinical success and was considered the... (Review)
Review
After introduction of the first commercial combined PET and/or CT technology in 2001, this diagnostic tool quickly became a clinical success and was considered the fastest growing diagnostic imaging technology ever. However, this technique is very dependent on the availability of positron emitting isotopes and radiochemistry to incorporate the radioactive isotopes into larger molecules of physiological interest. Within this review article a historical overview starting with the first applications of positron emitting isotopes in the 1930's is presented. Afterwards a more detailed presentation summarizing the physical basis and advancements in cyclotron technology is given. Radiochemical and/or pharmaceutical advancements are presented systematically for the most significant isotopes like O, N, C, F and Ga Besides these major PET isotopes, advancements of other radio-metals and future perspectives regarding application of new radionuclides will be discussed. Finally, very interesting new and compact accelerator technology and microfluidic chemical reaction approaches will be discussed. Especially, new compact accelerator technology might be new quantum leap within this radiodiagnostic technology and might result in even further prevalence, ultimately envisioned by the dose-on-demand concept that will be briefly discussed.
Topics: Cyclotrons; Humans; Positron-Emission Tomography; Radiochemistry; Radioisotopes; Radiopharmaceuticals
PubMed: 34836618
DOI: 10.1053/j.semnuclmed.2021.10.003 -
Problemy Endokrinologii Feb 2021Radiotheranostics is a radionuclide therapy based on the results of molecular imaging with various radiopharmaceuticals, allowing in vivo whole body imaging (SPECT,...
Radiotheranostics is a radionuclide therapy based on the results of molecular imaging with various radiopharmaceuticals, allowing in vivo whole body imaging (SPECT, PET), and then systemically and at the same time selectively acting on pathological metabolic processes caused by a pathological process. In recent years, thanks to advances in the development of nuclear medicine (an increase in the number of cyclotrons, SPECT / CT and PET / CT in medical institutions) and, particularly, novel radiopharmaceuticals - in the world, radiotheranostics is developing very rapidly. The emergence of new radioligands labelled by 177Lu, 131I, 225Ac and other radioisotopes in the world have initiated a large number of clinical trials of radioligand therapy of neuroendocrine and chromaffin tumors, prostate cancer, etc. Radiotherapy as a new and very promising direction of nuclear medicine and it is perfectly integrated into modern diagnostic algorithms in the field of endocrinology and oncology. Methods of intraoperative radionavigation make it possible to increase the efficiency and safety of surgical methods, external beam radiation therapy, and brachytherapy. In my opinion, the future of personalized medicine will be predominantly determined by the integration of radiotherapy, multimodal imaging, intraoperative navigation and existing/new methods of diagnosis and treatment, in combination with applied genomic and post-genomic technologies.
Topics: Actinium; Humans; Iodine Radioisotopes; Male; Radiopharmaceuticals
PubMed: 33586387
DOI: 10.14341/probl12731 -
EJNMMI Radiopharmacy and Chemistry Oct 2022The radiometal gallium-68 (Ga) is increasingly used in diagnostic positron emission tomography (PET), with Ga-labeled radiopharmaceuticals developed as potential... (Review)
Review
BACKGROUND
The radiometal gallium-68 (Ga) is increasingly used in diagnostic positron emission tomography (PET), with Ga-labeled radiopharmaceuticals developed as potential higher-resolution imaging alternatives to traditional Tc agents. In precision medicine, PET applications of Ga are widespread, with Ga radiolabeled to a variety of radiotracers that evaluate perfusion and organ function, and target specific biomarkers found on tumor lesions such as prostate-specific membrane antigen, somatostatin, fibroblast activation protein, bombesin, and melanocortin.
MAIN BODY
These Ga radiopharmaceuticals include agents such as [Ga]Ga-macroaggregated albumin for myocardial perfusion evaluation, [Ga]Ga-PLED for assessing renal function, [Ga]Ga-t-butyl-HBED for assessing liver function, and [Ga]Ga-PSMA for tumor imaging. The short half-life, favourable nuclear decay properties, ease of radiolabeling, and convenient availability through germanium-68 (Ge) generators and cyclotron production routes strongly positions Ga for continued growth in clinical deployment. This progress motivates the development of a set of common guidelines and standards for the Ga radiopharmaceutical community, and recommendations for centers interested in establishing Ga radiopharmaceutical production.
CONCLUSION
This review outlines important aspects of Ga radiopharmacy, including Ga production routes using a Ge/Ga generator or medical cyclotron, standardized Ga radiolabeling methods, quality control procedures for clinical Ga radiopharmaceuticals, and suggested best practices for centers with established or upcoming Ga radiopharmaceutical production. Finally, an outlook on Ga radiopharmaceuticals is presented to highlight potential challenges and opportunities facing the community.
PubMed: 36271969
DOI: 10.1186/s41181-022-00180-1 -
Mass Spectrometry Reviews Mar 2022Proteoforms contribute functional diversity to the proteome and aberrant proteoforms levels have been implicated in biological dysfunction and disease. Fourier-transform... (Review)
Review
Proteoforms contribute functional diversity to the proteome and aberrant proteoforms levels have been implicated in biological dysfunction and disease. Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS), with its ultrahigh mass-resolving power, mass accuracy, and versatile tandem MS capabilities, has empowered top-down, middle-down, and native MS-based approaches for characterizing proteoforms and their complexes in biological systems. Herein, we review the features which make FT-ICR MS uniquely suited for measuring proteoform mass with ultrahigh resolution and mass accuracy; obtaining in-depth proteoform sequence coverage with expansive tandem MS capabilities; and unambiguously identifying and localizing post-translational and noncovalent modifications. We highlight examples from our body of work in which we have quantified and comprehensively characterized proteoforms from cardiac and skeletal muscle to better understand conditions such as chronic heart failure, acute myocardial infarction, and sarcopenia. Structural characterization of monoclonal antibodies and their proteoforms by FT-ICR MS and emerging applications, such as native top-down FT-ICR MS and high-throughput top-down FT-ICR MS-based proteomics at 21 T, are also covered. Historically, the information gleaned from FT-ICR MS analyses have helped provide biological insights. We predict FT-ICR MS will continue to enable the study of proteoforms of increasing size from increasingly complex endogenous mixtures and facilitate the benchmarking of sensitive and specific assays for clinical diagnostics. © 2020 John Wiley & Sons Ltd. Mass Spec Rev.
Topics: Cyclotrons; Fourier Analysis; Mass Spectrometry; Protein Processing, Post-Translational; Proteome; Proteomics
PubMed: 32894796
DOI: 10.1002/mas.21653 -
Mass Spectrometry Reviews Mar 2022Research in the field of neurobiology and neurochemistry has seen a rapid expansion in the last several years due to advances in technologies and instrumentation,... (Review)
Review
Research in the field of neurobiology and neurochemistry has seen a rapid expansion in the last several years due to advances in technologies and instrumentation, facilitating the detection of biomolecules critical to the complex signaling of neurons. Part of this growth has been due to the development and implementation of high-resolution Fourier transform (FT) mass spectrometry (MS), as is offered by FT ion cyclotron resonance (FTICR) and Orbitrap mass analyzers, which improves the accuracy of measurements and helps resolve the complex biological mixtures often analyzed in the nervous system. The coupling of matrix-assisted laser desorption/ionization (MALDI) with high-resolution MS has drastically expanded the information that can be obtained with these complex samples. This review discusses notable technical developments in MALDI-FTICR and MALDI-Orbitrap platforms and their applications toward molecules in the nervous system, including sequence elucidation and profiling with de novo sequencing, analysis of post-translational modifications, in situ analysis, key advances in sample preparation and handling, quantitation, and imaging. Notable novel applications are also discussed to highlight key developments critical to advancing our understanding of neurobiology and providing insight into the exciting future of this field. © 2020 John Wiley & Sons Ltd. Mass Spec Rev.
Topics: Cyclotrons; Fourier Analysis; Neurobiology; Specimen Handling; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 33165982
DOI: 10.1002/mas.21661 -
Mass Spectrometry Reviews Mar 2022The set of all intra- and intermolecular interactions, collectively known as the interactome, is currently an unmet challenge for any analytical method, but if measured,... (Review)
Review
The set of all intra- and intermolecular interactions, collectively known as the interactome, is currently an unmet challenge for any analytical method, but if measured, could provide unparalleled insight on molecular function in living systems. Developments and applications of chemical cross-linking and high-performance mass spectrometry technologies are beginning to reveal details on how proteins interact in cells and how protein conformations and interactions inside cells change with phenotype or during drug treatment or other perturbations. A major contributor to these advances is Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) technology and its implementation with accurate mass measurements on cross-linked peptide-pair precursor and fragment ions to enable improved identification methods. However, these applications place increased demands on mass spectrometer performance in terms of high-resolution spectral acquisition rates for on-line MS experiments. Moreover, FT-ICR-MS also offers unique opportunities to develop and implement parallel ICR cells for multiplexed signal acquisition and the potential to greatly advance accurate mass acquisition rates for interactome studies. This review highlights our efforts to exploit accurate mass FT-ICR-MS technologies with chemical cross-linking and developments being pursued to realize parallel MS array capabilities that will further advance visualization of the interactome.
Topics: Cyclotrons; Fourier Analysis; Ions; Mass Spectrometry; Proteins
PubMed: 33289940
DOI: 10.1002/mas.21675 -
Molecular Imaging Feb 2010Rapid and widespread growth in the use of nuclear medicine for both diagnosis and therapy of disease has been the driving force behind burgeoning research interests in... (Review)
Review
Rapid and widespread growth in the use of nuclear medicine for both diagnosis and therapy of disease has been the driving force behind burgeoning research interests in the design of novel radiopharmaceuticals. Until recently, the majority of clinical and basic science research has focused on the development of 11C-, 13N-, 15O-, and 18F-radiopharmaceuticals for use with positron emission tomography (PET) and 99mTc-labeled agents for use with single-photon emission computed tomography (SPECT). With the increased availability of small, low-energy cyclotrons and improvements in both cyclotron targetry and purification chemistries, the use of "nonstandard" radionuclides is becoming more prevalent. This brief review describes the physical characteristics of 60 radionuclides, including beta+, beta-, gamma-ray, and alpha-particle emitters, which have the potential for use in the design and synthesis of the next generation of diagnostic and/or radiotherapeutic drugs. As the decay processes of many of the radionuclides described herein involve emission of high-energy gamma-rays, relevant shielding and radiation safety issues are also considered. In particular, the properties and safety considerations associated with the increasingly prevalent PET nuclides 64Cu, 68Ga, 86Y, 89Zr, and 124I are discussed.
Topics: Humans; Nuclear Medicine; Positron-Emission Tomography; Radiation, Ionizing; Radioisotopes; Radiopharmaceuticals; Radiotherapy; Tomography, Emission-Computed, Single-Photon
PubMed: 20128994
DOI: No ID Found -
Journal of Nuclear Medicine : Official... Jan 2021Theranostic strategies involve select radionuclides that allow diagnostic imaging and tailored radionuclide therapy in the same patient. An example of a Food and Drug...
Theranostic strategies involve select radionuclides that allow diagnostic imaging and tailored radionuclide therapy in the same patient. An example of a Food and Drug Administration-approved theranostic pair is the Ga- and Lu-labeled DOTATATE peptides, which are used to image neuroendocrine tumors, predict treatment response, and treat disease. However, when using radionuclides of 2 different elements, differences in the pharmacokinetic and pharmacodynamic profile of the agent can occur. Theranostic agents that incorporate the matched-pair radionuclides of scandium-Sc/Sc or Sc/Sc-would guarantee identical chemistries and pharmacologic profiles. The aim of this study was to investigate production of Sc via proton-induced nuclear reactions on titanium nuclei using a 24-MeV cyclotron. Aluminum, niobium, and tantalum target holders were used with titanium foils and pressed TiO to produce scandium radionuclides with proton energies of up to 24 MeV. Irradiated targets were digested using NHHF and HCl in a closed perfluoroalkoxy alkane vessel in 90 min. Scandium radionuclides were purified via ion-exchange chromatography using branched -tetra-2-ethylhexyldiglycolamide. The titanium target material was recovered via alkali precipitation with ammonia solution. Titanium foil and TiO were digested with an average efficiency of 98% ± 3% and 95% ± 1%, respectively. The typical digestion time was 45 min for titanium foil and 75 min for TiO The average scandium recovery was 94% ± 3%, and the average titanium recoveries from digested titanium foil and TiO after precipitation as TiO were 108% ± 8% and 104% ± 5% of initial mass, respectively. This work demonstrated a robust method for the cyclotron production of scandium radionuclides that could be used with natural or enriched TiO target material.
Topics: Biological Transport; Cell Line, Tumor; Cyclotrons; Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Prostate-Specific Antigen; Radiochemistry; Radioisotopes; Scandium; Titanium
PubMed: 32620699
DOI: 10.2967/jnumed.120.242941 -
Molecules (Basel, Switzerland) Aug 2022The production of reactor-based medical isotopes is fragile, which has meant supply shortages from time to time. This paper reviews alternative production methods in the... (Review)
Review
The production of reactor-based medical isotopes is fragile, which has meant supply shortages from time to time. This paper reviews alternative production methods in the form of cyclotrons, linear accelerators and neutron generators. Finally, the status of the production of medical isotopes in China is described.
Topics: China; Cyclotrons; Isotopes; Neutrons; Particle Accelerators; Radioisotopes
PubMed: 36014532
DOI: 10.3390/molecules27165294 -
Frontiers in Chemistry 2023Sc and Sc are both positron-emitting radioisotopes of scandium with suitable half-lives and favorable positron energies for clinical positron emission tomography (PET)...
Sc and Sc are both positron-emitting radioisotopes of scandium with suitable half-lives and favorable positron energies for clinical positron emission tomography (PET) imaging. Irradiation of isotopically enriched calcium targets has higher cross sections compared to titanium targets and higher radionuclidic purity and cross sections than natural calcium targets for reaction routes possible on small cyclotrons capable of accelerating protons and deuterons. In this work, we investigate the following production routes via proton and deuteron bombardment on CaCO and CaO target materials: Ca(d,n)Sc, Ca(p,n)Sc, Ca(d,n)Sc, Ca(p,n)Sc, and Ca(p,2n)Sc. Radiochemical isolation of the produced radioscandium was performed with extraction chromatography using branched DGA resin and apparent molar activity was measured with the chelator DOTA. The imaging performance of Sc and Sc was compared with F, Ga, and Cu on two clinical PET/CT scanners. The results of this work demonstrate that proton and deuteron bombardment of isotopically enriched CaO targets produce high yield and high radionuclidic purity Sc and Sc. Laboratory capabilities, circumstances, and budgets are likely to dictate which reaction route and radioisotope of scandium is chosen.
PubMed: 37179772
DOI: 10.3389/fchem.2023.1167783