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Pharmaceutics Jan 2022Over the last decade, targeted alpha therapy has demonstrated its high effectiveness in treating various oncological diseases. Lead-212, with a convenient half-life of... (Review)
Review
Over the last decade, targeted alpha therapy has demonstrated its high effectiveness in treating various oncological diseases. Lead-212, with a convenient half-life of 10.64 h, and daughter alpha-emitter short-lived Bi ( = 1 h), provides the possibility for the synthesis and purification of complex radiopharmaceuticals with minimum loss of radioactivity during preparation. As a benefit for clinical implementation, it can be milked from a radionuclide generator in different ways. The main approaches applied for these purposes are considered and described in this review, including chromatographic, solution, and other techniques to isolate Pb from its parent radionuclide. Furthermore, molecules used for lead's binding and radiochemical features of preparation and stability of compounds labeled with Pb are discussed. The results of preclinical studies with an estimation of therapeutic and tolerant doses as well as recently initiated clinical trials of targeted radiopharmaceuticals are presented.
PubMed: 35057083
DOI: 10.3390/pharmaceutics14010189 -
Pharmaceuticals (Basel, Switzerland) Jan 2017The favorable nuclear properties of rhenium-188 for therapeutic application are described, together with new methods for the preparation of high yield and stable Re... (Review)
Review
The favorable nuclear properties of rhenium-188 for therapeutic application are described, together with new methods for the preparation of high yield and stable Re radiopharmaceuticals characterized by the presence of the nitride rhenium core in their final chemical structure. Re is readily available from an W/Re generator system and a parallelism between the general synthetic procedures applied for the preparation of nitride technetium-99m and rhenium-188 theranostics radiopharmaceuticals is reported. Although some differences between the chemical characteristics of the two metallic nitrido fragments are highlighted, it is apparent that the same general procedures developed for the labelling of biologically active molecules with technetium-99m can be applied to rhenium-188 with minor modification. The availability of these chemical strategies, that allow the obtainment, in very high yield and in physiological condition, of Re radiopharmaceuticals, gives a new attractive prospective to employ this radionuclide for therapeutic applications.
PubMed: 28106830
DOI: 10.3390/ph10010012 -
Applied Radiation and Isotopes :... Dec 2020In order to determine the potential of Lu/Lu radionuclide generator in Lu production it is important to establish the technical needs that can lead to a clinically...
In order to determine the potential of Lu/Lu radionuclide generator in Lu production it is important to establish the technical needs that can lead to a clinically acceptable Lu product quality. In this work, a model that includes all the processes and the parameters affecting the performance of the Lu/Lu radionuclide generator has been developed. The model has been based on the use of a ligand to complex Lu ions, followed by the separation of the freed Lu ions. The dissociation kinetics of the Lu-ligand complex has been found to be the most crucial aspect governing the specific activity and Lu content of the produced Lu. The dissociation rate constants lower than 1*10 s would be required to lead to onsite Lu production with specific activity close to theoretical maximum of 4.1 TBq Lu/mg Lu and with Lu content of less than 0.01%. Lastly, the calculations suggest that more than one patient dose per week can be supplied for a period of up to 7 months on starting with the Lu produced using 3 g LuO target with 60% Lu enrichment. The requirements of the starting Lu activity production needs to be adapted depending on the required patient doses, and the technical specifications of the involved Lu-Lu separation process.
PubMed: 32961525
DOI: 10.1016/j.apradiso.2020.109261 -
Bioinorganic Chemistry and Applications 2016In vivo radionuclide generators make complex combinations of physical and chemical properties available for medical diagnostics and therapy. Perhaps the best-known in... (Review)
Review
In vivo radionuclide generators make complex combinations of physical and chemical properties available for medical diagnostics and therapy. Perhaps the best-known in vivo generator is Pb/Bi, which takes advantage of the extended half-life of Pb to execute a targeted delivery of the therapeutic short-lived -emitter Bi. Often, as in the case of Rb/Kr, chemical changes resulting from the transmutation of the parent are relied upon for diagnostic value. In other instances such as with extended alpha decay chains, chemical changes may lead to unwanted consequences. This article reviews some common and not-so-common in vivo generators with the purpose of understanding their value in medicine and medical research. This is currently relevant in light of a recent push for alpha emitters in targeted therapies, which often come with extended decay chains.
PubMed: 28058040
DOI: 10.1155/2016/6148357 -
Molecules (Basel, Switzerland) Feb 2023The β emitter, rhenium-188 (Re), has long been recognized as an attractive candidate for targeted cancer radionuclide therapy (TRNT). This transition metal shares... (Review)
Review
The β emitter, rhenium-188 (Re), has long been recognized as an attractive candidate for targeted cancer radionuclide therapy (TRNT). This transition metal shares chemical similarities with its congener element technetium, whose nuclear isomer technetium-99m (Tc) is the current workhorse of diagnostic nuclear medicine. The differences between these two elements have a significant impact on the radiolabelling methods and should always receive critical attention. This review aims to highlight what needs to be considered to design a successful radiopharmaceutical incorporating Re. Some of the most effective strategies for preparing therapeutic radiopharmaceuticals with Re are illustrated and rationalized using the concept of the inorganic functional group (core) and a simple ligand field theoretical model combined with a qualitative definition of frontiers orbitals. Of special interest are the Re(V) oxo and Re(V) nitrido functional groups. Suitable ligands for binding to these cores are discussed, successful clinical applications are summarized, and a prediction of viable future applications is presented. Rhenium-188 decays through the emission of a high energy beta particle (2.12 MeV max energy) and a half-life of 16.9 h. An ideal biological target would therefore be a high-capacity target site (transporters, potential gradients, tumour microenvironment) with less emphasis on saturable targets such as overexpressed receptors on smaller metastases.
Topics: Radiopharmaceuticals; Technetium; Radioisotopes; Rhenium
PubMed: 36771153
DOI: 10.3390/molecules28031487 -
Pharmaceutics Jun 2021A new two-column Ac/Bi generator was developed specifically for using Ac containing an impurity of long lived Ac. The parent Ac was retained on the first Actinide Resin...
A new two-column Ac/Bi generator was developed specifically for using Ac containing an impurity of long lived Ac. The parent Ac was retained on the first Actinide Resin column, while Bi was accumulated on the second column filled with AG MP-50 resin via continuous elution and decay of intermediate Fr. The Bi accumulation was realized in circulation mode which allowed a compact generator design. It was demonstrated that Bi could be quickly and effectively extracted from AG MP-50 in form of complexes with various chelating agents including DTPA and DOTA. The performance of the generator presented and a conventional single-column generator on the base of AG MP-50 was tested and both generators were loaded with Ac containing Ac impurity. The Bi generation efficiencies were comparable and greater than 70%, whereas the developed generator provided a deeper degree of purification of Bi from Ac isotopes and decay products of Ac.
PubMed: 34205580
DOI: 10.3390/pharmaceutics13060914 -
Current Radiopharmaceuticals 2023In recent years, there has been an increased interest in Ti/Sc generators as an onsite source of Sc for medical applications without needing a proximal cyclotron. The... (Review)
Review
In recent years, there has been an increased interest in Ti/Sc generators as an onsite source of Sc for medical applications without needing a proximal cyclotron. The relatively short half-life (3.97 hours) and high positron branching ratio (94.3%) of Sc make it a viable candidate for positron emission tomography (PET) imaging. This review discusses current Ti/Sc generator designs, focusing on their chemistry, drawbacks, post-elution processing, and relevant preclinical studies of the Sc for potential PET radiopharmaceuticals.
Topics: Radioisotopes; Radiopharmaceuticals; Radionuclide Generators; Titanium; Scandium; Positron-Emission Tomography
PubMed: 36372922
DOI: 10.2174/1874471016666221111154424 -
Cancers Dec 2021Developments throughout the history of nuclear medicine have involved improvements in both instrumentation and radionuclides, which have been intertwined.... (Review)
Review
Developments throughout the history of nuclear medicine have involved improvements in both instrumentation and radionuclides, which have been intertwined. Instrumentation developments always occurred during the search to improving devices' sensitivity and included advances in detector technology (with the introduction of cadmium zinc telluride and digital Positron Emission Tomography-PET-devices with silicon photomultipliers), design (total body PET) and configuration (ring-shaped, Single-Photon Emission Computed Tomography (SPECT), Compton camera). In the field of radionuclide development, we observed the continual changing of clinically used radionuclides, which is sometimes influenced by instrumentation technology but also driven by availability, patient safety and clinical questions. Some areas, such as tumour imaging, have faced challenges when changing radionuclides based on availability, when this produced undesirable clinical findings with the introduction of unclear focal uptakes and unspecific uptakes. On the other end of spectrum, further developments of PET technology have seen a resurgence in its use in nuclear cardiology, with rubidium-82 from strontium-82/rubidium-82 generators being the radionuclide of choice, moving away from SPECT nuclides thallium-201 and technetium-99m. These continuing improvements in both instrumentation and radionuclide development have helped the growth of nuclear medicine and its importance in the ever-evolving range of patient care options.
PubMed: 34944803
DOI: 10.3390/cancers13246183