دورية أكاديمية
In vivo [64Cu]CuCl2 PET imaging reveals activity of Dextran-Catechin on tumor copper homeostasis
| العنوان: | In vivo [64Cu]CuCl2 PET imaging reveals activity of Dextran-Catechin on tumor copper homeostasis |
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| المؤلفون: | Parmar, A, Pascali, G, Voli, F, Lerra, L, Yee, E, Ahmed-Cox, A, Kimpton, K, Cirillo, G, Arthur, A, Zahra, D, Rahardjo, G, Liu, GJ, Lengkeek, N, Saletta, F, Charil, A, Kavallaris, M, Vittorio, O |
| المصدر: | urn:ISSN:1838-7640 ; Theranostics, 8, 20, 5645-5659 |
| بيانات النشر: | Ivyspring International Publisher. |
| سنة النشر: | 2018 |
| المجموعة: | UNSW Sydney (The University of New South Wales): UNSWorks |
| مصطلحات موضوعية: | Cancer, Neuroblastoma, Rare Diseases, Neurosciences, Pediatric, Digestive Diseases, Biomedical Imaging, Bioengineering, 5.1 Pharmaceuticals, 5 Development of treatments and therapeutic interventions, Animals, Catechin, Cation Transport Proteins, Cell Line, Tumor, Copper, Copper Transporter 1, Dextrans, Female, Homeostasis, Humans, Immunohistochemistry, In Vitro Techniques, Mice, Inbred BALB C, Molecular Imaging, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Tissue Array Analysis, Anticancer drugs |
| الوصف: | Given the strong clinical evidence that copper levels are significantly elevated in a wide spectrum of tumors, copper homeostasis is considered as an emerging target for anticancer drug design. Monitoring copper levels in vivo is therefore of paramount importance when assessing the efficacy of copper-targeting drugs. Herein, we investigated the activity of the copper-targeting compound Dextran-Catechin by developing a [64Cu]CuCl2 PET imaging protocol to monitor its effect on copper homeostasis in tumors. Methods: Protein expression of copper transporter 1 (CTR1) in tissue microarrays representing 90 neuroblastoma patient tumors was assessed by immunohistochemistry. Western blotting analysis was used to study the effect of Dextran-Catechin on the expression of CTR1 in neuroblastoma cell lines and in tumors. A preclinical human neuroblastoma xenograft model was used to study anticancer activity of Dextran-Catechin in vivo and its effect on tumor copper homeostasis. PET imaging with [64Cu]CuCl2 was performed in such preclinical neuroblastoma model to monitor alteration of copper levels in tumors during treatment. Results: CTR1 protein was found to be highly expressed in patient neuroblastoma tumors by immunohistochemistry. Treatment of neuroblastoma cell lines with Dextran-Catechin resulted in decreased levels of glutathione and in downregulation of CTR1 expression, which caused a significant decrease of intracellular copper. No changes in CTR1 expression was observed in normal human astrocytes after Dextran-Catechin treatment. In vivo studies and PET imaging analysis using the neuroblastoma preclinical model revealed elevated [64Cu]CuCl2 retention in the tumor mass. Following treatment with Dextran-Catechin, there was a significant reduction in radioactive uptake, as well as reduced tumor growth. Ex vivo analysis of tumors collected from Dextran-Catechin treated mice confirmed the reduced levels of CTR1. Interestingly, copper levels in blood were not affected by treatment, demonstrating potential tumor specificity ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | http://purl.org/au-research/grants/nhmrc/APP1141582Test; http://hdl.handle.net/1959.4/unsworks_80699Test; https://unsworks.unsw.edu.au/bitstreams/fd228ad7-c7c4-4005-a3d0-d2b0c9cffa0a/downloadTest; https://doi.org/10.7150/thno.29840Test |
| DOI: | 10.7150/thno.29840 |
| الإتاحة: | https://doi.org/10.7150/thno.29840Test http://hdl.handle.net/1959.4/unsworks_80699Test https://unsworks.unsw.edu.au/bitstreams/fd228ad7-c7c4-4005-a3d0-d2b0c9cffa0a/downloadTest |
| حقوق: | open access ; https://purl.org/coar/access_right/c_abf2Test ; CC BY-NC ; https://creativecommons.org/licenses/by-nc/4.0Test/ ; free_to_read ; This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0Test/). See http://ivyspring.com/termsTest for full terms and conditions. |
| رقم الانضمام: | edsbas.5A6B5B82 |
| قاعدة البيانات: | BASE |
| DOI: | 10.7150/thno.29840 |
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