Radium 223

BACKGROUND & PURPOSE: Radium-223 (Ra223) improves survival in metastatic prostate cancer (mPC), but its impact on systemic immunity is unclear, and biomarkers of response are lacking. We examined markers of immunomodulatory activity during standard clinical Ra223 and studied the impact of Ra223 on response to immune checkpoint inhibition (ICI) in preclinical models. MATERIALS & METHODS: We conducted a single-arm biomarker study of Ra223 in 22 bone mPC patients...

Radium-223 dichloride is the first approved alpha particle-emitting radiopharmaceutical for patients with castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. A large percentage of intestinal enrichment and a slow clearance rate were the main causes of gastrointestinal adverse events after 223 RaCl2 administration. The molecular weight of sodium alginate in aqueous solution was determined to be 656 kDa. Sodium alginate exhibits a higher affinity for adsorbing Ra2+ compared to other metal ions belonging to the second main group...

BACKGROUND: Actinium-225 (225 Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of 225 Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world. METHODS: This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa. We pooled data of consecutive patients of any age and Eastern Cooperative Oncology Group performance status with histopathologically confirmed adenocarcinoma of the prostate who were treated with one or more cycles of 8 MBq 225 Ac-PSMA RLT administered intravenously for mCRPC...

Targeted alpha-particle therapy using radionuclides with alpha emission is a rapidly developing area in modern cancer treatment. To selectively deliver alpha-emitting isotopes to tumors, targeting vectors, including monoclonal antibodies, peptides, small molecule inhibitors, or other biomolecules, are attached to them, which ensures specific binding to tumor-related antigens and cell surface receptors. Although earlier studies have already demonstrated the anti-tumor potential of alpha-emitting radium (Ra) isotopes-Radium-223 and Radium-224 (223/224 Ra)-in the treatment of skeletal metastases, their inability to complex with target-specific moieties hindered application beyond bone targeting...

Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223 Ra]RaCl2 ) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223 Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 hours after intraperitoneal administration as an alternative to overcome the previous limitations...

Numerous technologies-with catalytic, therapeutic, and diagnostic applications-would benefit from improved chelation strategies for heavy alkaline earth elements: Ra2+ , Ba2+ , and Sr2+ . Unfortunately, chelating these metals is challenging because of their large size and weak polarizing power. We found 18-crown-6-tetracarboxylic acid ( H 4 COCO ) bound Ra2+ , Ba2+ , and Sr2+ to form M(H x COCO) x -2 . Upon isolating radioactive 223 Ra from its parent radionuclides (227 Ac and 227 Th), 223 Ra2+ reacted with the fully deprotonated COCO 4- chelator to generate Ra(COCO) 2- ( aq ) (log K Ra(COCO)2- = 5...

PURPOSE: The ADRRAD trial reported the safety and feasibility of the combination of external beam radiotherapy and radium-223 in the treatment of de novo bone metastatic prostate. This study aimed to determine if any biomarkers predictive of response to these treatments could be identified. EXPERIMENTAL DESIGN: 30 patients with newly diagnosed bone metastatic hormone sensitive prostate cancer were recruited to the ADRRAD trial. Blood samples were taken pre-treatment, before cycles 2 to 6 of radium-223, and 8 weeks and 6 months after treatment...

BACKGROUND: Most women with advanced breast cancer have skeletal metastases. Radium-223 is an alpha-emitting radionuclide that selectively targets areas of bone metastases. METHODS: Two double-blind, placebo-controlled studies of radium-223 were conducted in women with hormone receptor-positive (HR+), bone-predominant metastatic breast cancer. All patients received endocrine therapy (ET), as a single agent of the investigator's choice (Study A) or exemestane + everolimus (Study B)...

PURPOSE: Reliable biomarkers for response monitoring during radium-223 treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) are lacking. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), obtained from liquid biopsies, are shown to have prognostic value in mCRPC. The aim of this study was to determine the value of CTCs and ctDNA for response evaluation of radium-223. METHODS: In this prospective multicenter study, longitudinal blood draws and imaging were performed in 28 patients with mCRPC and predominantly bone disease, who were treated with radium-223...

The size of drug carriers strongly affects their biodistribution, tissue penetration, and cellular uptake in vivo . As a result, when such carriers are loaded with therapeutic compounds, their size can influence the treatment outcomes. For internal α-radionuclide therapy, the carrier size is particularly important, because short-range α-emitters should be delivered to tumor volumes at a high dose rate without any side effects, i.e. off-target irradiation and toxicity. In this work, we aim to evaluate and compare the therapeutic efficiency of calcium carbonate (CaCO3 ) microparticles (MPs, >2 μ m) and nanoparticles (NPs, <100 nm) labeled with radium-223 (223 Ra) for internal α-radionuclide therapy against 4T1 breast cancer...

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Driven by the anthropogenic activities associated with coastal settlements, eutrophication has become a global issue. Submarine groundwater discharge (SGD) is a significant continuous pathway for transporting nutrients from land to coastal waters, but its influence on eutrophication in Liaodong Bay (LDB) has received limited attention. In this study, radium isotopes and nutrient data from coastal waters were analyzed to evaluate the SGD flux and its implications for potential eutrophication in LDB. We found that the mean concentrations of dissolved inorganic nitrogen (DIN), phosphorous (DIP), and silicate (DSi) in groundwater were higher than those of seawater and river water...

BACKGROUND: The alpha-emitter radium-223 (223 Ra) is presently used in nuclear medicine for the palliative treatment of bone metastases from castration-resistant prostate cancer. This application arises from its advantageous decay properties and its intrinsic ability to accumulate in regions of high bone turnover when injected as a simple chloride salt. The commercial availability of [223 Ra]RaCl2 as a registered drug (Xofigo® ) is a further additional asset. MAIN BODY: The prospect of extending the utility of 223 Ra to targeted α-therapy of non-osseous cancers has garnered significant interest...

INTRODUCTION: Disseminated carcinomatosis of the bone marrow in prostate cancer is rare and has a poor prognosis. Although strong evidence suggests that novel hormonal agents improve the prognosis of metastatic prostate cancer, their effectiveness in cases of disseminated carcinomatosis of the bone marrow remains unclear. CASE PRESENTATION: We encountered two cases of prostate cancer with disseminated carcinomatosis of the bone marrow at the time of initial diagnosis...

INTRODUCTION: Bone-targeted therapies (BTTs) are integral to the management of bone metastases in metastatic castration-resistant prostate cancer (mCRPC). BTTs vary considerably in referral and drug access pathways and optimal BTT use requires multi-specialty consultation and supervision. Health quality improvement (HQI) has become the predominant framework to improve patient care in multidisciplinary settings. METHODS: HQI initiatives on use of BTT in mCRPC were developed and evaluated in five centers of a provincial cancer center network using Plan-Do-Study-Act (PDSA) methodology...

A radium-223 ion beam was delivered to an experiment from the electron cyclotron resonance ion source, ECR2, at the Argonne Tandem Linac Accelerator System (ATLAS). The radium-223 material was in a nitrate salt form within a vial, prior to being converted to a usable sputter sample. The sputter sample was produced using a new sample preparation method, where the radium nitrate was dissolved into a solution and pipetted onto pressed aluminum powder. This sample was then allowed to dry, distributing the radium-223 material throughout the sputter sample...

Radium-223 (223 Ra) is the first-in-class alpha-emitter to mediate tumor eradication, which is commonly thought to kill tumor cells by directly cleaving double-strand DNA. However, the immunogenic characteristics and cell death modalities triggered by 223 Ra remain unclear. Here, it is reported that the 223 Ra irradiation induces the pro-inflammatory damage-associated molecular patterns including calreticulin, HMGB1, and HSP70, hallmarks of tumor immunogenicity. Moreover, therapeutic 223 Ra retards tumor progression by triggering pyroptosis, an immunogenic cell death...

BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted...

223 Ra-dichloride (223 Ra) and 177 Lu-prostate-specific membrane antigen (PSMA) are approved treatments for metastatic castration-resistant prostate cancer (mCRPC). The safety and effectiveness of sequential use of 223 Ra and 177 Lu-PSMA in patients with mCRPC are not well described. This study aimed to evaluate 177 Lu-PSMA safety and efficacy in patients with mCRPC previously treated with 223 Ra. Methods: The radium→lutetium (RALU) study was a multicenter, retrospective, medical chart review. Participants had received at least 1 223 Ra dose and, in any subsequent therapy line, at least 1 177 Lu-PSMA dose...

Targeted α therapy (TAT) of soft-tissue cancers using the α particle-emitting radionuclide 223 Ra holds great potential because of its favorable nuclear properties, adequate availability, and established clinical use for treating metastatic prostate cancer of the bone. Despite these advantages, the use of 223 Ra has been largely overshadowed by other α emitters due to its challenging chelation chemistry. A key criterion that needs to be met for a radionuclide to be used in TAT is its stable attachment to a targeting vector via a bifunctional chelator...