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Journal of Applied Clinical Medical... Jan 2021March 2021 will mark the eightieth anniversary of targeted radionuclide therapy, recognizing the first use of radioactive iodine to treat thyroid disease by Dr. Saul...
March 2021 will mark the eightieth anniversary of targeted radionuclide therapy, recognizing the first use of radioactive iodine to treat thyroid disease by Dr. Saul Hertz on March 31, 1941. The breakthrough of Dr. Hertz and collaborator physicist Arthur Roberts was made possible by rapid developments in the fields of physics and medicine in the early twentieth century. Although diseases of the thyroid gland had been described for centuries, the role of iodine in thyroid physiology had been elucidated only in the prior few decades. After the discovery of radioactivity by Henri Becquerel in 1897, rapid advancements in the field, including artificial production of radioactive isotopes, were made in the subsequent decades. Finally, the diagnostic and therapeutic use of radioactive iodine was based on the tracer principal that was developed by George de Hevesy. In the context of these advancements, Hertz was able to conceive the potential of using of radioactive iodine to treat thyroid diseases. Working with Dr. Roberts, he obtained the experimental data and implemented it in the clinical setting. Radioiodine therapy continues to be a mainstay of therapy for hyperthyroidism and thyroid cancer. However, Hertz struggled to gain recognition for his accomplishments and to continue his work and, with his early death in 1950, his contributions have often been overlooked until recently. The work of Hertz and others provided a foundation for the introduction of other radionuclide therapies and for the development of the concept of theranostics.
Topics: Humans; Iodine; Iodine Radioisotopes; Precision Medicine; Thyroid Neoplasms
PubMed: 33533204
DOI: 10.1002/acm2.13175 -
Molecules (Basel, Switzerland) Aug 2022A search in PubMed revealed that 72 radionuclides have been considered for molecular or functional targeted radionuclide therapy. As radionuclide therapies increase in... (Review)
Review
A search in PubMed revealed that 72 radionuclides have been considered for molecular or functional targeted radionuclide therapy. As radionuclide therapies increase in number and variations, it is important to understand the role of the radionuclide and the various characteristics that can render it either useful or useless. This review focuses on the physical characteristics of radionuclides that are relevant for radionuclide therapy, such as linear energy transfer, relative biological effectiveness, range, half-life, imaging properties, and radiation protection considerations. All these properties vary considerably between radionuclides and can be optimised for specific targets. Properties that are advantageous for some applications can sometimes be drawbacks for others; for instance, radionuclides that enable easy imaging can introduce more radiation protection concerns than others. Similarly, a long radiation range is beneficial in targets with heterogeneous uptake, but it also increases the radiation dose to tissues surrounding the target, and, hence, a shorter range is likely more beneficial with homogeneous uptake. While one cannot select a collection of characteristics as each radionuclide comes with an unchangeable set, all the 72 radionuclides investigated for therapy-and many more that have not yet been investigated-provide numerous sets to choose between.
Topics: Half-Life; Radioisotopes
PubMed: 36080198
DOI: 10.3390/molecules27175429 -
ACS Nano Nov 2021Nanoparticles have unique properties that can be exploited for cancer diagnosis and therapy. Intravenously injected nanoparticles accumulate predominantly in organs of... (Review)
Review
Nanoparticles have unique properties that can be exploited for cancer diagnosis and therapy. Intravenously injected nanoparticles accumulate predominantly in organs of the mononuclear phagocytic system, in addition to localizing in tumors and at sites of inflammation and infection. Accumulation in the liver and spleen lowers nanoparticles' ability to target pathological sites and compromises their use for radionuclide therapy. As described by Lee . in this issue of , radionuclide retention in liver and spleen can be greatly reduced by using liposomes that are surface-modified with esterase-cleavable radionuclide anchors. Because esterase activity is high in healthy tissues and low in tumors, the authors found that liposome-associated radioactivity rapidly cleared from the body and remained high only in tumors. The resulting images had high contrast-to-background ratios and remarkable tumor delineation. In this Perspective, we discuss these advances from early detection, cancer diagnosis, radionuclide therapy, and theranostics points of view. We outline the current clinical landscape of radionuclide targeting, imaging and therapy, and reflect on the roles that nanoparticles can play in these applications. We highlight the potential of nanoparticles that are responsive to endogenous stimuli for intraoperative imaging and, particularly, for individualized and improved radionuclide treatment. Taking these advances into account, future studies exploring the robustness and the clinical feasibility of nanomedicine-based radiotheranostic probes are eagerly awaited.
Topics: Humans; Precision Medicine; Nanoparticles; Radioisotopes; Liposomes; Neoplasms; Esterases
PubMed: 34748314
DOI: 10.1021/acsnano.1c09139 -
Endocrine-related Cancer Mar 2021Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE has been approved for the treatment of gastroenteropancreatic NETs. An understanding of benefits and... (Review)
Review
Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE has been approved for the treatment of gastroenteropancreatic NETs. An understanding of benefits and risks is important for the appropriate implementation of this therapy. This review summarizes study data supporting the use of radiolabeled somatostatin analogs for the treatment of advanced NETs and highlights risks, including potential toxicities in specific populations. Key ongoing clinical trials, including randomized studies, are designed to better define the position of PRRT within the broader therapeutic landscape. Preclinical and early-phase human studies are focused on the development of novel somatostatin-receptor agonists and antagonists, new radionuclides, and radiosensitizing combination therapies.
Topics: Humans; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Positron-Emission Tomography; Radioisotopes; Radionuclide Imaging; Receptors, Somatostatin; Somatostatin
PubMed: 33608483
DOI: 10.1530/ERC-20-0360 -
International Journal of Molecular... Aug 2022Nearly 100,000 individuals are expected to be diagnosed with melanoma in the United States in 2022. Treatment options for late-stage metastatic disease up until the... (Review)
Review
Nearly 100,000 individuals are expected to be diagnosed with melanoma in the United States in 2022. Treatment options for late-stage metastatic disease up until the 2010s were few and offered only slight improvement to the overall survival. The introduction of B-RAF inhibitors and anti-CTLA4 and anti-PD-1/PD-L1 immunotherapies into standard of care brought measurable increases in the overall survival across all stages of melanoma. Despite the improvement in the survival statistics, patients treated with targeted therapies and immunotherapies are subject to very serious side effects, the development of drug resistance, and the high costs of treatment. This leaves room for the development of novel approaches as well as for the exploration of novel combination therapies for the treatment of metastatic melanoma. One such approach is targeting melanin pigment with radionuclide therapy. Advances in melanin-targeting radionuclide therapy of melanoma can be viewed from two spheres: (1) radioimmunotherapy (RIT) and (2) radiolabeled small molecules. The investigation of mechanisms of the action and efficacy of targeting melanin in melanoma treatment by RIT points to the involvement of the immune system such as complement dependent cytotoxicity. The combination of RIT with immunotherapy presents synergistic killing in mouse melanoma models. The field of radiolabeled small molecules is focused on radioiodinated compounds that have the ability to cross the cellular membranes to access intracellular melanin and can be applied in both therapy and imaging as theranostics. Clinical applications of targeting melanin with radionuclide therapies have produced encouraging results and clinical work is on-going. Continued work on targeting melanin with radionuclide therapy as a monotherapy, or possibly in combination with standard of care agents, has the potential to strengthen the current treatment options for melanoma patients.
Topics: Animals; Immunotherapy; Melanins; Melanoma; Mice; Radioimmunotherapy; Radioisotopes
PubMed: 36076924
DOI: 10.3390/ijms23179520 -
European Journal of Nuclear Medicine... May 2022
Topics: Albumins; Fibroblasts; Gelatinases; Humans; Radioisotopes; Serine Endopeptidases
PubMed: 35332379
DOI: 10.1007/s00259-022-05766-0 -
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 -
Biomaterials Oct 2018Pretargeted nuclear imaging and radiotherapy have recently attracted increasing attention for diagnosis and treatment of cancer with nanomedicines. This is because it... (Review)
Review
Pretargeted nuclear imaging and radiotherapy have recently attracted increasing attention for diagnosis and treatment of cancer with nanomedicines. This is because it conceptually offers better imaging contrast and therapeutic efficiency while reducing the dose to radiosensitive tissues compared to conventional strategies. In conventional imaging and radiotherapy, a directly radiolabeled nano-sized vector is administered and allowed to accumulate in the tumor, typically on a timescale of several days. In contrast, pretargeting is based on a two-step approach. First, a tumor-accumulating vector carrying a tag is administered followed by injection of a fast clearing radiolabeled agent that rapidly recognizes the tag of the tumor-bound vector in vivo. Therefore, pretargeting circumvents the use of long-lived radionuclides that is a necessity for sufficient tumor accumulation and target-to-background ratios using conventional approaches. In this review, we give an overview of recent advances in pretargeted imaging strategies. We will critically reflect on the advantages and disadvantages of current state-of-the-art conventional imaging approaches and compare them to pretargeted strategies. We will discuss the pretargeted imaging concept and the involved chemistry. Finally, we will discuss the steps forward in respect to clinical translation, and how pretargeted strategies could be applied to improve state-of-the-art radiotherapeutic approaches.
Topics: Nanomedicine; Radioisotopes; Theranostic Nanomedicine
PubMed: 30007471
DOI: 10.1016/j.biomaterials.2018.06.021 -
Drug Delivery Dec 2020Nowadays, emerging radiolabeled nanosystems are revolutionizing medicine in terms of diagnostics, treatment, and theranostics. These radionuclides include polymeric... (Review)
Review
Nowadays, emerging radiolabeled nanosystems are revolutionizing medicine in terms of diagnostics, treatment, and theranostics. These radionuclides include polymeric nanoparticles (NPs), liposomal carriers, dendrimers, magnetic iron oxide NPs, silica NPs, carbon nanotubes, and inorganic metal-based nanoformulations. Between these nano-platforms, polymeric NPs have gained attention in the biomedical field due to their excellent properties, such as their surface to mass ratio, quantum properties, biodegradability, low toxicity, and ability to absorb and carry other molecules. In addition, NPs are capable of carrying high payloads of radionuclides which can be used for diagnostic, treatment, and theranostics depending on the radioactive material linked. The radiolabeling process of nanoparticles can be performed by direct or indirect labeling process. In both cases, the most appropriate must be selected in order to keep the targeting properties as preserved as possible. In addition, radionuclide therapy has the advantage of delivering a highly concentrated absorbed dose to the targeted tissue while sparing the surrounding healthy tissues. Said another way, radioactive polymeric NPs represent a promising prospect in the treatment and diagnostics of cardiovascular diseases such as cardiac ischemia, infectious diseases such as tuberculosis, and other type of cancer cells or tumors.
Topics: Animals; Drug Carriers; Drug Delivery Systems; Humans; Nanoparticles; Neoplasms; Polymers; Radioisotopes
PubMed: 33118416
DOI: 10.1080/10717544.2020.1837296 -
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