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alpha emmiters

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Robert Coleman
Bone metastases are common in advanced malignancy and, despite the developments in both anticancer and bone-targeted therapies in recent years, new therapeutic strategies are still needed. Traditionally, radioisotopes have been rarely used in part owing to concerns about bone marrow toxicity that limits retreatment and may prevent safe administration of subsequent chemotherapy. Radium-223 dichloride (Ra-223) is a calcium mimetic that binds preferentially to newly formed bone in areas of bone metastases, is the first alpha-emitting radionuclide to be developed for clinical use, and is approved for treatment of castration-resistant prostate cancer and symptomatic bone metastases...
March 2016: Seminars in Nuclear Medicine
Min-Yuan Chang, Jonathan Seideman, Stavroula Sofou
Targeted alpha-particle emitters are promising therapeutics for micrometastatic disease. Actinium-225 has a 10-day half-life and generates a total of four alpha-particles per parent decay rendering (225)Ac an attractive candidate for alpha-therapy. For cancer cells with low surface expression levels of molecular targets, targeting strategies of (225)Ac using radiolabeled carriers of low specific radioactivities (such as antibodies) may not deliver enough alpha-particle emitters at the targeted cancer cells to result in killing...
June 2008: Bioconjugate Chemistry
J V Rojas, J D Woodward, N Chen, A J Rondinone, C H Castano, S Mirzadeh
INTRODUCTION: Targeted alpha therapy (TAT) has the potential for killing micro-metastases with minimum collateral damage to surrounding healthy tissue. In-vivo generator radionuclides, such as(223)Ra, (225)Ra, and (225)Ac, are of special interest for radiotherapeutic applications as they emit multiple α-particles during their decay. Utilizing appropriate carriers capable of retaining both the parent radioisotope as well as daughter products is important for the effective delivery of the radioisotope to the tumor site while mitigating global in vivo radiotoxicity...
July 2015: Nuclear Medicine and Biology
Cigdem Soydal, Elgin Ozkan, Serap Akyurek, Nuriye Ozlem Kucuk
We present pretreatment Ga prostate-specific membrane antigen (PSMA) PET/CT and posttreatment Lu-PSMA whole-body scintigraphy images of a 60-year-old patient with metastatic prostate cancer who is dramatically responding to Lu-PSMA treatment.
February 2016: Clinical Nuclear Medicine
Mutahir Tunio, Mushabbab Al Asiri, Abdulrehman Al Hadab, Yasser Bayoumi
BACKGROUND: A meta-analysis was conducted to assess the impact of radiopharmaceuticals (RPs) in castration-resistant prostate cancer (CRPC) on pain control, symptomatic skeletal events (SSEs), toxicity profile, quality of life (QoL), and overall survival (OS). MATERIALS AND METHODS: The PubMed/MEDLINE, CANCERLIT, EMBASE, Cochrane Library database, and other search engines were searched to identify randomized controlled trials (RCTs) comparing RPs with control (placebo or radiation therapy) in metastatic CRPC...
2015: Drug Design, Development and Therapy
Oliver Sartor
No abstract text is available yet for this article.
September 2015: Clinical Advances in Hematology & Oncology: H&O
John L Humm, Oliver Sartor, Chris Parker, Oyvind S Bruland, Roger Macklis
The element radium (Ra) was discovered by the Curies in 1898 and within a decade was in broad scientific testing for the management of several forms of cancer. The compound was known to give rise to a series of both high-energy particulate and penetrating γ-emissions. The latter found an important role in early 20th century brachytherapy applications, but the short-range α-particles seemed much less useful. Although highly cytotoxic when released within a few cell diameters of critical cell nuclei, the dense double-strand break damage was poorly repaired, and concerns regarding treatment-related toxicities and secondary malignancies halted clinical development...
April 1, 2015: International Journal of Radiation Oncology, Biology, Physics
P G Turner, J M O'Sullivan
Osseous metastases are a source of significant morbidity for patients with a variety of cancers. Radiotherapy is well established as an effective means of palliating symptoms associated with such metastases. The role of external beam radiotherapy is limited where sites of metastases are numerous and widespread. Low linear energy transfer (LET) radionuclides have been utilized to allow targeted delivery of radiotherapy to disparate sites of disease, with evidence of palliative benefit. More recently, the bone targeting, high LET radionuclide (223)Ra has been shown to not only have a palliative effect but also a survival prolonging effect in metastatic, castration-resistant prostate cancer with bone metastases...
June 2015: British Journal of Radiology
Chadwick L Wright, J Paul Monk, Douglas A Murrey, Nathan C Hall
Radium-223 ((223)Ra) dichloride is an approved intravenous radiotherapy for patients with osseous metastases from castration-resistant prostate cancer (CRPC). In addition to the therapeutic alpha radiation, there is additional (223)Ra radiation generated which produces photons that can be imaged with conventional gamma cameras. No studies have evaluated real-time and quality imaging during intravenous (223)Ra administration to verify systemic circulation and exclude (223)Ra extravasation at the injection site...
2015: BioMed Research International
Seth R Blacksburg, Matthew R Witten, Jonathan A Haas
Metastatic castrate-resistant prostate cancer (CRPC) refers to the disease state in which metastatic prostate cancer fails to respond to androgen deprivation therapy (ADT). This can be manifest as a rising PSA, increase in radiographically measurable disease, or progression of clinical disease. Roughly 90 % of men with metastatic prostate cancer have bone metastases, which is a predictor of both morbidity and mortality. Historically, treatment has been palliative, consisting of external beam radiation therapy (EBRT) and pharmacological analgesics for pain control and osteoclast inhibitors, such as bisphosphonates and denosumab to mitigate skeletal-related events...
March 2015: Current Treatment Options in Oncology
Hossein Jadvar, Sudha Challa, David I Quinn, Peter S Conti
OBJECTIVES: We report our 1-year postapproval clinical experience with Radium-223 dichloride for treatment of castrate-resistant prostate cancer with bone metastases. METHODS: The clinical courses of the first 25 patients treated were reviewed retrospectively. Incidence of hematologic, gastrointestinal, and other adverse events were identified, including those events that led to cessation or delay in treatment. Alterations in bone pain and serum alkaline phosphatase and prostate-specific antigen (PSA) levels were evaluated...
June 2015: Cancer Biotherapy & Radiopharmaceuticals
Oladapo Yeku, Susan F Slovin
INTRODUCTION: Prostate cancer metastatic to bone is a cause of significant morbidity and mortality. Bone pain and other skeletal events negatively impact the quality of life in patients who might otherwise be functioning well. As such, there has been intense interest in the development of strategies and pharmaceuticals to address this problem. AREAS COVERED: The authors reviewed the current literature for articles relevant to metastatic prostate cancer, clinical radiopharmaceuticals, castrate-resistant prostate cancer and development of Radium-223 ...
May 2015: Expert Opinion on Drug Metabolism & Toxicology
Tu D Dan, Harriet B Eldredge-Hindy, Jean Hoffman-Censits, Jianqing Lin, William K Kelly, Leonard G Gomella, Costas D Lallas, Edouard J Trabulsi, Mark D Hurwitz, Adam P Dicker, Robert B Den
PURPOSE/OBJECTIVES: Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases. Initial studies investigating Radium-223 primarily used nonsteroidal first-generation antiandrogens. Since that time, newer antiandrogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer. It has been suggested that the rational combination of these newly approved agents with Radium-223 may lead to improved response rates and clinical outcomes...
February 25, 2015: American Journal of Clinical Oncology
Neal D Shore
Radium-223 dichloride (radium-223) is an important therapeutic option for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no visceral disease. The unique mechanism of action of this first-in-class alpha-emitting radiopharmaceutical underlies its favorable safety profile and low incidence of myelosuppression. In the pivotal phase 3 ALpharadin in SYMptomatic Prostate CAncer Patients study, radium-223 reduced the risk of death by 30% and prolonged time to first symptomatic skeletal event by 5...
April 2015: Urology
Shane McGann, Evan R Horton
OBJECTIVE: To review and evaluate the clinical trial efficacy and safety of radium 223 ((223)Ra) along with its place in therapy in men with castration-resistant prostate cancer (CRPC). DATA SOURCES: A literature search in PubMed/MEDLINE (up to October 2014) was performed using various combinations of the terms radium, hormone-refractory prostate cancer, and castration-resistant prostate cancer. The New Drug Application Medical, Pharmacology, and Clinical Pharmacology and Biopharmaceutics Reviews for radium (223)Ra dichloride were also utilized...
April 2015: Annals of Pharmacotherapy
Alain S Abi-Ghanem, Mary A McGrath, Heather A Jacene
Bone metastases are associated with increased morbidity and poor prognosis in castration-resistant prostate cancer. Since 2010, 5 systemic therapies for metastatic castration-resistant prostate cancer have been approved by the US Food and Drug Administration based on an improvement in overall survival, offering alternatives to docetaxel, a chemotherapeutic agent with modest effect and significant toxicity. These systemic treatments belong to different classes of medication such as immunotherapy, hormonal therapy, chemotherapy, and radionuclide therapy...
January 2015: Seminars in Nuclear Medicine
Raymond N Dansereau
On May 15, 2013, Bayer Healthcare Pharmaceuticals announced that it had received marketing approval for the therapeutic radioactive medication radium Ra 223 dichloride injection (Xofigo; Ra 223). The product acquisition and distribution process for hospital-based nuclear pharmacies and nuclear medicine services is unlike any other. The product is distributed as a low-risk compounded sterile preparation through a single compounding nuclear pharmacy located in Denver, Colorado, pursuant to a prescription. This model for drug distribution and delivery to the user institution has implications for product quality, patient privacy, and delineation of professional responsibilities...
November 2014: Annals of Pharmacotherapy
Jann Mortensen, Liselotte Højgaard
The alpha emitter Radium-223 ((22)3Ra-Cl2) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone refractory prostate cancer. More than 1,000 patients have been included in clinical phase I-III tests showing significant reduction in alkaline phosphatase- and PSA level and prolonged survival. Adverse events are usually mild to moderate and comprise gastrointestinal and myelotoxic symptoms. Intravenously administered (22)3Ra-Cl2 (half-life 11.4 days) will likely be given every four weeks for six treatments to out-patients...
July 21, 2014: Ugeskrift for Laeger
Brian Wan-Chi Tse, Lidija Jovanovic, Colleen Coyne Nelson, Paul de Souza, Carl Andrew Power, Pamela Joan Russell
The mainstay therapeutic strategy for metastatic castrate-resistant prostate cancer (CRPC) continues to be androgen deprivation therapy usually in combination with chemotherapy or androgen receptor targeting therapy in either sequence, or recently approved novel agents such as Radium 223. However, immunotherapy has also emerged as an option for the treatment of this disease following the approval of sipuleucel-T by the FDA in 2010. Immunotherapy is a rational approach for prostate cancer based on a body of evidence suggesting these cancers are inherently immunogenic and, most importantly, that immunological interventions can induce protective antitumour responses...
2014: BioMed Research International
G von Amsberg, P Stroelin, C Bokemeyer, T Steuber
Metastasized castration-resistant prostate cancer (mCRPC) is defined by disease progression despite androgen depletion therapy (ADT). While until recently a life-prolonging effect could only be demonstrated for the taxane docetaxel, various alternative therapeutic options based on different mechanisms of action are available today: CYP17-inhibitor abiraterone and antiandrogen enzalutamide target the androgen receptor-signaling pathway, which maintains a crucial role in mCRPC. Cabazitxel - a semisynthetic taxane derivate - is the only second line chemotherapy, which results in a prolongation of overall survival to date...
October 2014: Deutsche Medizinische Wochenschrift
2015-04-15 04:00:25
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