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Theranostics 2021Despite numerous clinical trials and pre-clinical developments, the treatment of glioblastoma (GB) remains a challenge. The current survival rate of GB averages one... (Review)
Review
Despite numerous clinical trials and pre-clinical developments, the treatment of glioblastoma (GB) remains a challenge. The current survival rate of GB averages one year, even with an optimal standard of care. However, the future promises efficient patient-tailored treatments, including targeted radionuclide therapy (TRT). Advances in radiopharmaceutical development have unlocked the possibility to assess disease at the molecular level allowing individual diagnosis. This leads to the possibility of choosing a tailored, targeted approach for therapeutic modalities. Therapeutic modalities based on radiopharmaceuticals are an exciting development with great potential to promote a personalised approach to medicine. However, an effective targeted radionuclide therapy (TRT) for the treatment of GB entails caveats and requisites. This review provides an overview of existing nuclear imaging and TRT strategies for GB. A critical discussion of the optimal characteristics for new GB targeting therapeutic radiopharmaceuticals and clinical indications are provided. Considerations for target selection are discussed, i.e. specific presence of the target, expression level and pharmacological access to the target, with particular attention to blood-brain barrier crossing. An overview of the most promising radionuclides is given along with a validation of the relevant radiopharmaceuticals and theranostic agents (based on small molecules, peptides and monoclonal antibodies). Moreover, toxicity issues and safety pharmacology aspects will be presented, both in general and for the brain in particular.
Topics: Glioblastoma; Humans; Precision Medicine; Radioisotopes; Radiopharmaceuticals
PubMed: 34335972
DOI: 10.7150/thno.56639 -
Annals of Surgical Oncology Sep 2020Neuroendocrine tumors are becoming increasingly prevalent, with many patients presenting with or developing metastatic disease to the liver. (Review)
Review
BACKGROUND
Neuroendocrine tumors are becoming increasingly prevalent, with many patients presenting with or developing metastatic disease to the liver.
METHODS
In this landmark series paper, we highlight the critical studies that have defined the surgical management of neuroendocrine tumor liver metastases, as well as several randomized control trials which have investigated strategies for systemic control of metastatic disease.
RESULTS
Liver-directed surgical approaches and locally ablative procedures are recommended for patients with limited, resectable, and in some cases, nonresectable tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, chemoembolization, and radioembolization, offer another approach for management in patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising therapy for patients with hepatic and/or extrahepatic metastases. Various systemic medical therapies are also available as adjunct or definitive therapy for patients with metastatic disease.
CONCLUSIONS
This article reviews current data regarding management of neuroendocrine liver metastases and highlights areas for future study.
Topics: Chemoembolization, Therapeutic; Humans; Liver Neoplasms; Neuroendocrine Tumors; Radioisotopes; Randomized Controlled Trials as Topic; Tumor Burden
PubMed: 32632880
DOI: 10.1245/s10434-020-08787-x -
International Journal of Molecular... May 2019In the last two decades, various nanomaterials have attracted increasing attention in medical science owing to their unique physical and chemical characteristics.... (Review)
Review
In the last two decades, various nanomaterials have attracted increasing attention in medical science owing to their unique physical and chemical characteristics. Incorporating radionuclides into conventionally used nanomaterials can confer useful additional properties compared to the original material. Therefore, various radionuclides have been used to synthesize functional nanomaterials for biomedical applications. In particular, several α- or β-emitter-labeled organic and inorganic nanoparticles have been extensively investigated for efficient and targeted cancer treatment. This article reviews recent progress in cancer therapy using radiolabeled nanomaterials including inorganic, polymeric, and carbon-based materials and liposomes. We first provide an overview of radiolabeling methods for preparing anticancer agents that have been investigated recently in preclinical studies. Next, we discuss the therapeutic applications and effectiveness of α- or β-emitter-incorporated nanomaterials in animal models and the emerging possibilities of these nanomaterials in cancer therapy.
Topics: Animals; Humans; Nanostructures; Radioisotopes
PubMed: 31083402
DOI: 10.3390/ijms20092323 -
Seminars in Oncology Aug 2018Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is now approved for patients with advanced gastroenteropancreatic neuroendocrine tumors (NET), and it is... (Review)
Review
Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is now approved for patients with advanced gastroenteropancreatic neuroendocrine tumors (NET), and it is therefore important to understand the efficacy and safety of PRRT in this patient population. PRRT efficacy and safety outcomes have frequently been summarized for patient populations with gastroenteropancreatic NET, but not specifically in patients with pancreatic NET (panNET). The pivotal phase 3 trial of Lu-DOTATATE PRRT in NET was restricted to patients with a midgut primary site. No phase 3 trial data on PRRT treatment outcomes are currently available for the panNET patient population. This review presents the available evidence for panNET treatment outcomes with PRRT and demonstrates that the available data favor PRRT as a modality for this NET primary site. However, several other therapies for advanced panNET are currently available, and the sequencing and combination of PRRT with these other therapies is set to become the big challenge for the future of panNET management. Patient, tumor, and logistical factors (tumor burden, expression of somatostatin receptors, availability of PRRT, patient preferences, and concerns over long-term toxicity) need to be taken into consideration when selecting therapy.
Topics: Humans; Intestinal Neoplasms; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Radioisotopes; Stomach Neoplasms
PubMed: 30539715
DOI: 10.1053/j.seminoncol.2018.08.004 -
Journal of Nuclear Medicine : Official... Jan 2005Response and toxicity prediction is essential to rational implementation of cancer therapy. The biologic effects of radionuclide therapy are mediated via a well-defined... (Review)
Review
Response and toxicity prediction is essential to rational implementation of cancer therapy. The biologic effects of radionuclide therapy are mediated via a well-defined physical quantity, the absorbed dose, which is defined as the energy absorbed per unit mass of tissue. The concepts, basic definitions, and different approaches to the clinical implementation of absorbed dose estimation are reviewed in this article. Ongoing efforts to improve the accuracy of dosimetry calculations are discussed, as well as studies examining the relationship between absorbed dose and response. Particular attention is placed on the marrow and kidney as dose-limiting organs. Finally, the potential role of radiobiologic modeling in helping to account for differences in dose rate and spatial distribution are reviewed. A treatment planning approach to radionuclide therapy will eventually require incorporation of biologic and radiobiologic considerations. Until such methods are developed and validated, absorbed dose remains an important variable--but still one of several--likely to predict response in an individual patient.
Topics: Algorithms; Animals; Body Burden; Energy Transfer; Humans; Models, Biological; Neoplasms; Practice Patterns, Physicians'; Radioisotopes; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Relative Biological Effectiveness; Software
PubMed: 15653648
DOI: No ID Found -
The British Journal of Radiology Nov 2018Theranostics and its principles: pre-treatment selection of patients who are most likely to benefit from treatment by the use of a related, specific diagnostic test are... (Review)
Review
Theranostics and its principles: pre-treatment selection of patients who are most likely to benefit from treatment by the use of a related, specific diagnostic test are integral to the treatment of patients with neuroendocrine tumours (NETs). This is due to NETs' important, but variable, somatostatin receptor (SSTR) expression, their heterogeneity and variation in site of primary and rate of progression. Only patients whose tumours have sufficient expression of SSTRs will benefit from SSTR-based radionuclide therapy and demonstrating this expression prior to therapy is essential. This article provides a relevant overview of NETs and the multiple facets of SSTR based theranostics, including imaging and therapy radionuclides; clinical efficacy and toxicity; patient selection and treatment and finally emerging radiopharmaceuticals and newer clinical applications.
Topics: Aged; Humans; Male; Middle Aged; Neuroendocrine Tumors; Patient Selection; Radioisotopes; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Theranostic Nanomedicine; Treatment Outcome
PubMed: 30102557
DOI: 10.1259/bjr.20180108 -
Journal of Labelled Compounds &... Jul 2018The exquisite specificity of antibodies and antibody fragments renders them excellent agents for targeted delivery of radionuclides. Radiolabeled antibodies and... (Review)
Review
The exquisite specificity of antibodies and antibody fragments renders them excellent agents for targeted delivery of radionuclides. Radiolabeled antibodies and fragments have been successfully used for molecular imaging and radioimmunotherapy (RIT) of cell surface targets in oncology and immunology. Protein engineering has been used for antibody humanization essential for clinical applications, as well as optimization of important characteristics including pharmacokinetics, biodistribution, and clearance. Although intact antibodies have high potential as imaging and therapeutic agents, challenges include long circulation time in blood, which leads to later imaging time points post-injection and higher blood absorbed dose that may be disadvantageous for RIT. Using engineered fragments may address these challenges, as size reduction and removal of Fc function decreases serum half-life. Radiolabeled fragments and pretargeting strategies can result in high contrast images within hours to days, and a reduction of RIT toxicity in normal tissues. Additionally, fragments can be engineered to direct hepatic or renal clearance, which may be chosen based on the application and disease setting. This review discusses aligning the physical properties of radionuclides (positron, gamma, beta, alpha, and Auger emitters) with antibodies and fragments and highlights recent advances of engineered antibodies and fragments in preclinical and clinical development for imaging and therapy.
Topics: Animals; Antibodies; Humans; Isotope Labeling; Physical Phenomena; Protein Engineering; Radioimmunotherapy; Radioisotopes
PubMed: 29537104
DOI: 10.1002/jlcr.3622 -
Clinical Medicine (London, England) 2006
Review
Topics: Antibodies, Monoclonal; Bone and Bones; Humans; Pain; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals; Radiotherapy Dosage; Recurrence; Thyroid Gland; Thyroid Neoplasms; Thyrotoxicosis
PubMed: 16826856
DOI: 10.7861/clinmedicine.6-3-249 -
Journal of Labelled Compounds &... Jul 2018Recent advances in molecular characterization of tumors have made possible the emergence of new types of cancer therapies where traditional cytotoxic drugs and... (Review)
Review
Recent advances in molecular characterization of tumors have made possible the emergence of new types of cancer therapies where traditional cytotoxic drugs and nonspecific chemotherapy can be complemented with targeted molecular therapies. One of the main revolutionary treatments is the use of monoclonal antibodies (mAbs) that selectively target the disseminated tumor cells while sparing normal tissues. mAbs and related therapeutics can be efficiently radiolabeled with a wide range of radionuclides to facilitate preclinical and clinical studies. Non-invasive molecular imaging techniques, such as Positron Emission Tomography (PET), using radiolabeled mAbs provide useful information on the whole-body distribution of the biomolecules, which may enable patient stratification, diagnosis, selection of targeted therapies, evaluation of treatment response, and prediction of dose limiting tissue and adverse effects. In addition, when mAbs are labeled with therapeutic radionuclides, the combination of immunological and radiobiological cytotoxicity may result in enhanced treatment efficacy. The pharmacokinetic profile of antibodies demands the use of long half-life isotopes for longitudinal scrutiny of mAb biodistribution and precludes the use of well-stablished short half-life isotopes. Herein, we review the most promising PET radiometals with chemical and physical characteristics that make the appealing for mAb labeling, highlighting those with theranostic radioisotopes.
Topics: Animals; Antibodies, Monoclonal; Humans; Isotope Labeling; Metals; Positron-Emission Tomography; Radioisotopes
PubMed: 29341227
DOI: 10.1002/jlcr.3607 -
The Quarterly Journal of Nuclear... Jun 2015Beta-emitting radionuclides are not able to kill isolated tumor cells disseminated in the body, even if a high density of radiolabeled molecules can be targeted at the... (Review)
Review
Beta-emitting radionuclides are not able to kill isolated tumor cells disseminated in the body, even if a high density of radiolabeled molecules can be targeted at the surface of these cells because the vast majority of emitted electrons deliver their energy outside the targeted cells. Alpha-particle emitting radionuclides may overcome this limitation. It is thus of primary importance to test and validate the radionuclide of choice, the most appropriate carrier molecule and the most promising clinical indication. Four α-particle emitting radionuclides have been or are clinically tested in phase I studies namely 213Bi, 225Ac, 212Pb and 211At. Clinical safety has been documented and encouraging efficacy has been shown for some of them (213Bi and 211At). 211At has been the most studied and could be the most promising radionuclide but 225Ac and 212Pb are also of potential great interest. Any carrier molecule that has been labeled with β-emitting radionuclides could be labeled with alpha particle-emitting radionuclide using, for some of them, the same chelating agents. However, the physical half-life of the radionuclide should match the biological half-life of the radioconjugate or its catabolites. Finally everybody agrees, based on the quite short range of alpha particles, on the fact that the clinical indications for alpha-immunotherapy should be limited to the situation of disseminated minimal residual diseases made of small clusters of malignant cells or isolated tumor cells.
Topics: Alpha Particles; Drug Carriers; Evidence-Based Medicine; Humans; Immunotherapy; Isotope Labeling; Neoplasms; Radioisotopes
PubMed: 25752501
DOI: No ID Found