-
Lancet (London, England) Sep 1999Nuclear medicine therapy uses unsealed radioactive sources for the selective delivery of radiation to tumours or target organs. For benign disorders such as... (Review)
Review
Nuclear medicine therapy uses unsealed radioactive sources for the selective delivery of radiation to tumours or target organs. For benign disorders such as thyrotoxicosis and arthritis radionuclide therapy provides an alternative to surgery or medical treatment. In cancer treatment, it often combines the advantage of target selectivity (like brachytherapy or external beam radiotherapy) with that of being systemic, as with chemotherapy, and it may be used as part of a therapeutic strategy with curative intent or for disease control and palliation. Toxicity is generally limited to the haematopoietic tissue and few side-effects are observed. When cure is feasible, the long-term consequences of radionuclide therapy (eg, fertility disorders and leukaemia or other secondary cancers) do compare favourably with the risks associated with and accepted for chemotherapy and radiotherapy.
Topics: Arthritis; Brachytherapy; Humans; Neoplasms; Radioisotopes; Radiotherapy; Thyrotoxicosis; Treatment Outcome
PubMed: 10489968
DOI: 10.1016/S0140-6736(99)06002-X -
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 -
Current Radiopharmaceuticals Sep 2013Radionuclide therapy (RNT) based on the concept of delivering cytotoxic levels of radiation to disease sites is one of the rapidly growing fields of nuclear medicine.... (Review)
Review
Radionuclide therapy (RNT) based on the concept of delivering cytotoxic levels of radiation to disease sites is one of the rapidly growing fields of nuclear medicine. Unlike conventional external beam therapy, RNT targets diseases at the cellular level rather than on a gross anatomical level. This concept is a blend of a tracer moiety that mediates a site specific accumulation followed by induction of cytotoxicity with the short-range biological effectiveness of particulate radiations. Knowledge of the biochemical reactions taking place at cellular levels has stimulated the development of sophisticated molecular carriers, catalyzing a shift towards using more specific targeting radiolabelled agents. There is also improved understanding of factors of importance for choice of appropriate radionuclides based on availability, the types of emissions, linear energy transfer (LET), and physical half-life. This article discusses the applications of radionuclide therapy for treatment of cancer as well as other diseases. The primary objective of this review is to provide an overview on the role of radionuclide therapy in the treatment of different diseases such as polycythaemia, thyroid malignancies, metastatic bone pain, radiation synovectomy, hepatocellular carcinoma (HCC), neuroendocrine tumors (NETs), non-Hodgkin's lymphoma (NHL) and others. In addition, recent developments on the systematic approach in designing treatment regimens as well as recent progress, challenges and future perspectives are discussed. An examination of the progress of radionuclide therapy indicates that although a rapid stride has been made for treating hematological tumors, the development for treating solid tumors has, so far, been limited. However, the emergence of novel tumor-specific targeting agents coupled with successful characterization of new target structures would be expected to pave the way for future treatment for such tumors.
Topics: Bone Diseases; Electrons; Humans; Linear Energy Transfer; Nanoparticles; Neoplasms; Neuroendocrine Tumors; Nuclear Medicine; Pain Management; Polycythemia; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals; Radiotherapy
PubMed: 24059327
DOI: 10.2174/18744710113066660023 -
Wiener Medizinische Wochenschrift (1946) Oct 2012For decades, Iodine-131 has been used for the treatment of patients with thyroid cancer. In recent years, increasingly, other radiopharmaceuticals are in clinical use in... (Review)
Review
For decades, Iodine-131 has been used for the treatment of patients with thyroid cancer. In recent years, increasingly, other radiopharmaceuticals are in clinical use in the treatment of various malignant diseases. Although in principle these therapies-as in all applications of radionuclides-special radiation protection measures are required, a separate nuclear medicine therapy department is not necessary in many cases due to the lower or lack of gamma radiation. In the following article, four different radionuclide therapies are more closely presented which are emerging in the last years. One of them is the "Peptide Receptor Radionuclide Therapy," the so-called PRRT in which radiolabeled somatostatin (SST)-receptor(R) ligands are used in patients with neuroendocrine tumors. On the basis of radiolabeled antibodies against CD20-positive cells, the so-called radioimmunotherapy is used in the treatment of certain forms of malignant lymphoma. In primary or secondary liver tumors, the (90)Y-labeled particles can be administered. Last but not the least, the palliative approach of bone-seeking radiopharmaceuticals is noted in patients with painful bone metastases.
Topics: Bone Neoplasms; Gamma Rays; Humans; Iodine Radioisotopes; Liver Neoplasms; Lymphoma; Neoplasms; Neuroendocrine Tumors; Palliative Care; Radiation Protection; Radioimmunotherapy; Radioisotopes; Receptors, Somatostatin; Thyroid Neoplasms; Yttrium Radioisotopes
PubMed: 22815123
DOI: 10.1007/s10354-012-0128-6 -
European Journal of Nuclear Medicine 1991Apart from its use in endocrinology and rheumatology, therapeutic nuclear medicine is developing rapidly as an additional treatment modality in oncology. Many different... (Review)
Review
Apart from its use in endocrinology and rheumatology, therapeutic nuclear medicine is developing rapidly as an additional treatment modality in oncology. Many different specific tumour-seeking radiopharmaceuticals are being applied both for diagnostic scintigraphy and treatment, using multiple routes and mechanisms to target radionuclides at tumours. After a brief introduction of some basic principles of radionuclide targeting, the therapeutic radiopharmaceuticals available are reviewed according to the accumulation site in relation to the cell nucleus; the results of their current clinical use for therapy are also reviewed. The response observed to a number of these applications, the non-invasiveness of the procedure and the relative lack of toxicity and late effects in comparison with chemotherapy and external beam radiotherapy make radionuclide therapy an attractive and realistic alternative in the management of malignant disease, as well as in the treatment of a few benign disorders.
Topics: Antibodies, Monoclonal; Brachytherapy; Humans; Neoplasms; Radioisotopes
PubMed: 1879447
DOI: 10.1007/BF02258432 -
Clinical Cancer Research : An Official... Sep 2022The development of immunotherapy, in particular immune checkpoint inhibitors (ICI), has revolutionized cancer treatment in the past decades. However, its efficacy is... (Review)
Review
The development of immunotherapy, in particular immune checkpoint inhibitors (ICI), has revolutionized cancer treatment in the past decades. However, its efficacy is still limited to subgroups of patients with cancer. Therefore, effective treatment combination strategies are needed. Here, radiotherapy is highly promising, as it can induce immunogenic cell death, triggering the release of pro-inflammatory cytokines, thereby creating an immunogenic phenotype and sensitizing tumors to ICI. Recently, targeted radionuclide therapy (TRT) has attained significant interest for cancer treatment. In this approach, a tumor-targeting radiopharmaceutical is used to specifically deliver a therapeutic radiation dose to all tumor cells, including distant metastatic lesions, while limiting radiation exposure to healthy tissue. However, fundamental differences between TRT and conventional radiotherapy make it impossible to directly extrapolate the biological effects from conventional radiotherapy to TRT. In this review, we present a comprehensive overview of studies investigating the immunomodulatory effects of TRT and the efficacy of combined TRT-ICI treatment. Preclinical studies have evaluated a variety of murine cancer models in which α- or β-emitting radionuclides were directed to a diverse set of targets. In addition, clinical trials are ongoing to assess safety and efficacy of combined TRT-ICI in patients with cancer. Taken together, research indicates that combining TRT and ICI might improve therapeutic response in patients with cancer. Future research has to disclose what the optimal conditions are in terms of dose and treatment schedule to maximize the efficacy of this combined approach.
Topics: Animals; Combined Modality Therapy; Immune Checkpoint Inhibitors; Immunotherapy; Mice; Neoplasms; Radioisotopes
PubMed: 35471557
DOI: 10.1158/1078-0432.CCR-21-4332 -
Current Medicinal Chemistry 2020Receptor-targeted image-guided Radionuclide Therapy (TRT) is increasingly recognized as a promising approach to cancer treatment. In particular, the potential for... (Review)
Review
Receptor-targeted image-guided Radionuclide Therapy (TRT) is increasingly recognized as a promising approach to cancer treatment. In particular, the potential for clinical translation of receptor-targeted alpha-particle therapy is receiving considerable attention as an approach that can improve outcomes for cancer patients. Higher Linear-energy Transfer (LET) of alpha-particles (compared to beta particles) for this purpose results in an increased incidence of double-strand DNA breaks and improved-localized cancer-cell damage. Recent clinical studies provide compelling evidence that alpha-TRT has the potential to deliver a significantly more potent anti-cancer effect compared with beta-TRT. Generator-produced 212Pb (which decays to alpha emitters 212Bi and 212Po) is a particularly promising radionuclide for receptor-targeted alpha-particle therapy. A second attractive feature that distinguishes 212Pb alpha-TRT from other available radionuclides is the possibility to employ elementallymatched isotope 203Pb as an imaging surrogate in place of the therapeutic radionuclide. As direct non-invasive measurement of alpha-particle emissions cannot be conducted using current medical scanner technology, the imaging surrogate allows for a pharmacologically-inactive determination of the pharmacokinetics and biodistribution of TRT candidate ligands in advance of treatment. Thus, elementally-matched 203Pb labeled radiopharmaceuticals can be used to identify patients who may benefit from 212Pb alpha-TRT and apply appropriate dosimetry and treatment planning in advance of the therapy. In this review, we provide a brief history on the use of these isotopes for cancer therapy; describe the decay and chemical characteristics of 203/212Pb for their use in cancer theranostics and methodologies applied for production and purification of these isotopes for radiopharmaceutical production. In addition, a medical physics and dosimetry perspective is provided that highlights the potential of 212Pb for alpha-TRT and the expected safety for 203Pb surrogate imaging. Recent and current preclinical and clinical studies are presented. The sum of the findings herein and observations presented provide evidence that the 203Pb/212Pb theranostic pair has a promising future for use in radiopharmaceutical theranostic therapies for cancer.
Topics: Bismuth; Humans; Lead Radioisotopes; Neoplasms; Precision Medicine; Radioisotopes; Radiopharmaceuticals; Tissue Distribution
PubMed: 32720598
DOI: 10.2174/0929867327999200727190423 -
Annals of Nuclear Medicine Apr 1998Therapeutic nuclear medicine is rapidly developing as an additional treatment modality in oncology. Its unique characteristics are the systemic, yet selective delivery... (Review)
Review
Therapeutic nuclear medicine is rapidly developing as an additional treatment modality in oncology. Its unique characteristics are the systemic, yet selective delivery of radiation doses in target tissues, its non-invasiveness, the relative lack of immediate and late side effects, and the advantage that uptake and retention in the tumor can be pre-assessed by tracer studies. Many different tumor seeking radiopharmaceuticals are being used for therapy by different routes and a variety of targeting mechanisms. The current clinical role of radionuclide therapy is briefly reviewed, as well as more general aspects and considerations, such as mechanisms for tumor targeting, the choice of radionuclide labels, radiopharmacy, drug delivery, radiation protection, dosimetry and toxicity.
Topics: Drug Carriers; Humans; Neoplasms; Radioisotopes; Radionuclide Imaging; Radiopharmaceuticals
PubMed: 9637275
DOI: 10.1007/BF03164831 -
Nuclear Medicine Communications Aug 1999
Topics: Data Collection; Humans; Neoplasms; Radioisotopes; Radiotherapy; United Kingdom
PubMed: 10451875
DOI: 10.1097/00006231-199908000-00001 -
Cancer Science Jun 2022Theranostics is a term coined by combining the words "therapeutics" and "diagnostics," referring to single chemical entities developed to deliver therapy and diagnosis... (Review)
Review
Theranostics is a term coined by combining the words "therapeutics" and "diagnostics," referring to single chemical entities developed to deliver therapy and diagnosis simultaneously. Neuroendocrine tumors are rare cancers that occur in various organs of the body, and they express neuroendocrine factors such as chromogranin A and somatostatin receptor. Somatostatin analogs bind to somatostatin receptor, and when combined with diagnostic radionuclides, such as gamma-emitters, are utilized for diagnosis of neuroendocrine tumor. Somatostatin receptor scintigraphy when combined with therapeutic radionuclides, such as beta-emitters, are effective in treating neuroendocrine tumor as peptide receptor radionuclide therapy. Somatostatin receptor scintigraphy and peptide receptor radionuclide therapy are some of the most frequently used and successful theranostics for neuroendocrine tumor. In Japan, radiopharmaceuticals are regulated under a complex law system, creating a significant drug lag, which is a major public concern. It took nearly 10 years to obtain the approval for somatostatin receptor scintigraphy and peptide receptor radionuclide therapy use by the Japanese government. In 2021, Lu-DOTATATE (Lutathera), a drug for peptide receptor radionuclide therapy, was covered by insurance in Japan. In this review, we summarize the history of the development of neuroendocrine tumor theranostics and theranostics in general, as therapeutic treatment for cancer in the future. Furthermore, we briefly address the Japanese point of view regarding the development of new radiopharmaceuticals.
Topics: Humans; Neuroendocrine Tumors; Positron-Emission Tomography; Precision Medicine; Radioisotopes; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin
PubMed: 35271754
DOI: 10.1111/cas.15327