دورية أكاديمية
Improved Radium-223 Therapy with Combination Epithelial Sodium Channel Blockade.
| العنوان: | Improved Radium-223 Therapy with Combination Epithelial Sodium Channel Blockade. |
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| المؤلفون: | Abou DS; Washington University in St. Louis School of Medicine, United States., Fears A; Washington University in St. Louis School of Medicine, United States., Summer L; Washington University in St. Louis School of Medicine, United States., Longtine M; Washington University in St. Louis School of Medicine, United States., Benabdallah N; Washington University in St. Louis School of Medicine, United States., Riddle RC; Johns Hopkins University., Ulmert D; University of California Los Angeles., Michalski J; Washington University in St. Louis School of Medicine, United States., Wahl RL; Washington University in St. Louis School of Medicine, United States., Chesner D; Johns Hopkins University., Doucet M; Johns Hopkins University., Zachos N; Johns Hopkins University., Simons B; Baylor College of Medicine., Thorek DL; Washington University in St. Louis School of Medicine, United States. |
| المصدر: | Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2021 Apr 09. Date of Electronic Publication: 2021 Apr 09. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Society of Nuclear Medicine Country of Publication: United States NLM ID: 0217410 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1535-5667 (Electronic) Linking ISSN: 01615505 NLM ISO Abbreviation: J Nucl Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Reston, VA : Society of Nuclear Medicine Original Publication: [Chicago, Ill.] : S.N. Turiel & Assoc. |
| مستخلص: | Background: Radium-223 dichloride ([ 223 Ra]RaCl2) is the first approved alpha particle-emitting therapy and is indicated for treatment of bone metastatic castrate resistant prostate cancer. Approximately half of the dose is absorbed into the gastrointestinal (GI) tract within minutes of administration, limiting disease-site uptake and contributing to toxicity. Here, we investigate the role of enteric ion channels and their modulation for improved therapeutic efficacy and reduced side effects. Methods: Utilizing primary human duodenal organoids (enteroids) as in vitro models of the functional GI epithelium, we found that Amiloride (ENaC blocker) and NS-1619 (K+ channel activator) presented significant effects in 223 Ra membranal transport. The radioactive drug distribution was evaluated for lead combinations in vivo, and in osteosarcoma and prostate cancer models. Results: Amiloride shifted 223 Ra uptake in vivo from the gut, to nearly double the uptake at sites of bone remodeling. Bone tumor growth inhibition with the combination as measured by bioluminescent and X-ray imaging was significantly greater than single agents alone, and the combination resulted in no weight loss. Conclusion: This combination of approved agents may be readily implemented as a clinical approach to improve outcomes of bone metastatic cancer patients with the benefit of ameliorated tolerability. (Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.) |
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| معلومات مُعتمدة: | R01 CA201035 United States CA NCI NIH HHS; R01 CA229893 United States CA NCI NIH HHS; R01 CA240711 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: Bone; Gastrointestinal; Radionuclide Therapy; Radium-223; amiloride; bone; gastrointestinal; ion channel |
| تواريخ الأحداث: | Date Created: 20210410 Latest Revision: 20240222 |
| رمز التحديث: | 20240223 |
| مُعرف محوري في PubMed: | PMC8612198 |
| DOI: | 10.2967/jnumed.121.261977 |
| PMID: | 33837069 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1535-5667 |
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| DOI: | 10.2967/jnumed.121.261977 |