Imaging Neurotensin Receptor in Prostate Cancer With Cu-Labeled Neurotensin Analogs
Introduction: Neurotensin receptor 1 (NTR-1) is expressed and activated in prostate cancer cells. In this study, we explore the NTR expression in normal mouse tissues and study the positron emission tomography (PET) imaging of NTR in prostate cancer models. Materials and Methods: Three 64 Cu chelato...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-08-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.1177/1536012117711369 |
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| author | Huaifu Deng MD Hui Wang PhD He Zhang MD Mengzhe Wang MS Ben Giglio PhD Xiaofen Ma MD Guihua Jiang MD Hong Yuan PhD Zhanhong Wu PhD Zibo Li PhD |
| author_facet | Huaifu Deng MD Hui Wang PhD He Zhang MD Mengzhe Wang MS Ben Giglio PhD Xiaofen Ma MD Guihua Jiang MD Hong Yuan PhD Zhanhong Wu PhD Zibo Li PhD |
| author_sort | Huaifu Deng MD |
| collection | DOAJ |
| description | Introduction: Neurotensin receptor 1 (NTR-1) is expressed and activated in prostate cancer cells. In this study, we explore the NTR expression in normal mouse tissues and study the positron emission tomography (PET) imaging of NTR in prostate cancer models. Materials and Methods: Three 64 Cu chelators (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid [DOTA], 1,4,7-triazacyclononane-N,N′,N″-triacetic acid [NOTA], or AmBaSar) were conjugated to an NT analog. Neurotensin receptor binding affinity was evaluated using cell binding assay. The imaging profile of radiolabeled probes was compared in well-established NTR + HT-29 tumor model. Stability of the probes was tested. The selected agents were further evaluated in human prostate cancer PC3 xenografts. Results: All 3 NT conjugates retained the majority of NTR binding affinity. In HT-29 tumor, all agents demonstrated prominent tumor uptake. Although comparable stability was observed, 64 Cu-NOTA-NT and 64 Cu-AmBaSar-NT demonstrated improved tumor to background contrast compared with 64 Cu-DOTA-NT. Positron emission tomography/computed tomography imaging of the NTR expression in PC-3 xenografts showed high tumor uptake of the probes, correlating with the in vitro Western blot results. Blocking experiments further confirmed receptor specificity. Conclusions: Our results demonstrated that 64 Cu-labeled neurotensin analogs are promising imaging agents for NTR-positive tumors. These agents may help us identify NTR-positive lesions and predict which patients and individual tumors are likely to respond to novel interventions targeting NTR-1. |
| format | Article |
| id | doaj-art-1ac0a898a5a84cb5b9d5d721fe434ee8 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2017-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-1ac0a898a5a84cb5b9d5d721fe434ee82025-01-02T02:57:58ZengSAGE PublishingMolecular Imaging1536-01212017-08-011610.1177/1536012117711369Imaging Neurotensin Receptor in Prostate Cancer With Cu-Labeled Neurotensin AnalogsHuaifu Deng MD0Hui Wang PhD1He Zhang MD2Mengzhe Wang MS3Ben Giglio PhD4Xiaofen Ma MD5Guihua Jiang MD6Hong Yuan PhD7Zhanhong Wu PhD8Zibo Li PhD9 PET/CT Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China Department of Radiology, Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Radiology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China Department of Radiology, Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Radiology, Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Medical Imaging, Provincial People’s Hospital, Guangzhou, China Department of Medical Imaging, Provincial People’s Hospital, Guangzhou, China Department of Radiology, Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Radiology, Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Radiology, Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAIntroduction: Neurotensin receptor 1 (NTR-1) is expressed and activated in prostate cancer cells. In this study, we explore the NTR expression in normal mouse tissues and study the positron emission tomography (PET) imaging of NTR in prostate cancer models. Materials and Methods: Three 64 Cu chelators (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid [DOTA], 1,4,7-triazacyclononane-N,N′,N″-triacetic acid [NOTA], or AmBaSar) were conjugated to an NT analog. Neurotensin receptor binding affinity was evaluated using cell binding assay. The imaging profile of radiolabeled probes was compared in well-established NTR + HT-29 tumor model. Stability of the probes was tested. The selected agents were further evaluated in human prostate cancer PC3 xenografts. Results: All 3 NT conjugates retained the majority of NTR binding affinity. In HT-29 tumor, all agents demonstrated prominent tumor uptake. Although comparable stability was observed, 64 Cu-NOTA-NT and 64 Cu-AmBaSar-NT demonstrated improved tumor to background contrast compared with 64 Cu-DOTA-NT. Positron emission tomography/computed tomography imaging of the NTR expression in PC-3 xenografts showed high tumor uptake of the probes, correlating with the in vitro Western blot results. Blocking experiments further confirmed receptor specificity. Conclusions: Our results demonstrated that 64 Cu-labeled neurotensin analogs are promising imaging agents for NTR-positive tumors. These agents may help us identify NTR-positive lesions and predict which patients and individual tumors are likely to respond to novel interventions targeting NTR-1.https://doi.org/10.1177/1536012117711369 |
| spellingShingle | Huaifu Deng MD Hui Wang PhD He Zhang MD Mengzhe Wang MS Ben Giglio PhD Xiaofen Ma MD Guihua Jiang MD Hong Yuan PhD Zhanhong Wu PhD Zibo Li PhD Imaging Neurotensin Receptor in Prostate Cancer With Cu-Labeled Neurotensin Analogs Molecular Imaging |
| title | Imaging Neurotensin Receptor in Prostate Cancer With Cu-Labeled Neurotensin Analogs |
| title_full | Imaging Neurotensin Receptor in Prostate Cancer With Cu-Labeled Neurotensin Analogs |
| title_fullStr | Imaging Neurotensin Receptor in Prostate Cancer With Cu-Labeled Neurotensin Analogs |
| title_full_unstemmed | Imaging Neurotensin Receptor in Prostate Cancer With Cu-Labeled Neurotensin Analogs |
| title_short | Imaging Neurotensin Receptor in Prostate Cancer With Cu-Labeled Neurotensin Analogs |
| title_sort | imaging neurotensin receptor in prostate cancer with cu labeled neurotensin analogs |
| url | https://doi.org/10.1177/1536012117711369 |
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