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Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models
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Zeitschriftentitel: | Clinical Cancer Research |
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Personen und Körperschaften: | , , , , , , , , , , , |
In: | Clinical Cancer Research, 25, 2019, 1, S. 188-200 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
American Association for Cancer Research (AACR)
|
Schlagwörter: |
author_facet |
Zhang, Mo Kobayashi, Naoko Zettlitz, Kirstin A. Kono, Evelyn A. Yamashiro, Joyce M. Tsai, Wen-Ting K. Jiang, Ziyue K. Tran, Chau P. Wang, Chung Guan, Johnny Wu, Anna M. Reiter, Robert E. Zhang, Mo Kobayashi, Naoko Zettlitz, Kirstin A. Kono, Evelyn A. Yamashiro, Joyce M. Tsai, Wen-Ting K. Jiang, Ziyue K. Tran, Chau P. Wang, Chung Guan, Johnny Wu, Anna M. Reiter, Robert E. |
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author |
Zhang, Mo Kobayashi, Naoko Zettlitz, Kirstin A. Kono, Evelyn A. Yamashiro, Joyce M. Tsai, Wen-Ting K. Jiang, Ziyue K. Tran, Chau P. Wang, Chung Guan, Johnny Wu, Anna M. Reiter, Robert E. |
spellingShingle |
Zhang, Mo Kobayashi, Naoko Zettlitz, Kirstin A. Kono, Evelyn A. Yamashiro, Joyce M. Tsai, Wen-Ting K. Jiang, Ziyue K. Tran, Chau P. Wang, Chung Guan, Johnny Wu, Anna M. Reiter, Robert E. Clinical Cancer Research Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models Cancer Research Oncology |
author_sort |
zhang, mo |
spelling |
Zhang, Mo Kobayashi, Naoko Zettlitz, Kirstin A. Kono, Evelyn A. Yamashiro, Joyce M. Tsai, Wen-Ting K. Jiang, Ziyue K. Tran, Chau P. Wang, Chung Guan, Johnny Wu, Anna M. Reiter, Robert E. 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-18-1382 <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>The inability to intraoperatively distinguish primary tumor, as well as lymphatic spread, increases the probability of positive surgical margins, tumor recurrence, and surgical toxicity. The goal of this study was to develop a tumor-specific optical probe for real-time fluorescence-guided surgery.</jats:p> </jats:sec> <jats:sec> <jats:title>Experimental Design:</jats:title> <jats:p>A humanized antibody fragment against PSCA (A11 minibody, A11 Mb) was conjugated with a near-infrared fluorophore, IRDye800CW. The integrity and binding of the probe to PSCA were confirmed by gel electrophoresis, size-exclusion chromatography, and flow cytometry, respectively. The ability of the probe to detect tumor-infiltrated lymph nodes and metastatic lesions was evaluated in 2 xenograft models, as well as in transgenic mice expressing human PSCA (hPSCA). An invasive intramuscular model was utilized to evaluate the efficacy of the A11 Mb-IRDye800CW-guided surgery.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>A11 Mb was successfully conjugated with IRDye800CW and retained specific binding to PSCA. In vivo imaging showed maximal signal-to-background ratios at 48 hours. The A11 Mb-IRDye800CW specifically detected PSCA-positive primary tumors, tumor-infiltrated lymph nodes, and distant metastases with high contrast. Fluorescence guidance facilitated more complete tumor resection, reduced tumor recurrence, and improved overall survival, compared with conventional white light surgery. The probe successfully identified primary orthotopic tumors and metastatic lesions in hPSCA transgenic mice.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Real-time fluorescence image–guided surgery with A11 Mb-IRDye800CW enabled detection of lymph node metastases and positive surgical margins, facilitated more complete tumor removal, and improved survival, compared with white light surgery. These results may be translatable into clinical practice to improve surgical and patient outcomes.</jats:p> </jats:sec> Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models Clinical Cancer Research |
doi_str_mv |
10.1158/1078-0432.ccr-18-1382 |
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Online Free |
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Medizin |
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ElectronicArticle |
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American Association for Cancer Research (AACR), 2019 |
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American Association for Cancer Research (AACR), 2019 |
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1078-0432 1557-3265 |
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1078-0432 1557-3265 |
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zhang2019nearinfrareddyelabeledantiprostatestemcellantigenminibodyenablesrealtimefluorescenceimagingandtargetedsurgeryintranslationalmousemodels |
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2019 |
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American Association for Cancer Research (AACR) |
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Clinical Cancer Research |
source_id |
49 |
title |
Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models |
title_unstemmed |
Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models |
title_full |
Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models |
title_fullStr |
Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models |
title_full_unstemmed |
Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models |
title_short |
Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models |
title_sort |
near-infrared dye-labeled anti-prostate stem cell antigen minibody enables real-time fluorescence imaging and targeted surgery in translational mouse models |
topic |
Cancer Research Oncology |
url |
http://dx.doi.org/10.1158/1078-0432.ccr-18-1382 |
publishDate |
2019 |
physical |
188-200 |
description |
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Purpose:</jats:title>
<jats:p>The inability to intraoperatively distinguish primary tumor, as well as lymphatic spread, increases the probability of positive surgical margins, tumor recurrence, and surgical toxicity. The goal of this study was to develop a tumor-specific optical probe for real-time fluorescence-guided surgery.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Experimental Design:</jats:title>
<jats:p>A humanized antibody fragment against PSCA (A11 minibody, A11 Mb) was conjugated with a near-infrared fluorophore, IRDye800CW. The integrity and binding of the probe to PSCA were confirmed by gel electrophoresis, size-exclusion chromatography, and flow cytometry, respectively. The ability of the probe to detect tumor-infiltrated lymph nodes and metastatic lesions was evaluated in 2 xenograft models, as well as in transgenic mice expressing human PSCA (hPSCA). An invasive intramuscular model was utilized to evaluate the efficacy of the A11 Mb-IRDye800CW-guided surgery.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results:</jats:title>
<jats:p>A11 Mb was successfully conjugated with IRDye800CW and retained specific binding to PSCA. In vivo imaging showed maximal signal-to-background ratios at 48 hours. The A11 Mb-IRDye800CW specifically detected PSCA-positive primary tumors, tumor-infiltrated lymph nodes, and distant metastases with high contrast. Fluorescence guidance facilitated more complete tumor resection, reduced tumor recurrence, and improved overall survival, compared with conventional white light surgery. The probe successfully identified primary orthotopic tumors and metastatic lesions in hPSCA transgenic mice.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions:</jats:title>
<jats:p>Real-time fluorescence image–guided surgery with A11 Mb-IRDye800CW enabled detection of lymph node metastases and positive surgical margins, facilitated more complete tumor removal, and improved survival, compared with white light surgery. These results may be translatable into clinical practice to improve surgical and patient outcomes.</jats:p>
</jats:sec> |
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author | Zhang, Mo, Kobayashi, Naoko, Zettlitz, Kirstin A., Kono, Evelyn A., Yamashiro, Joyce M., Tsai, Wen-Ting K., Jiang, Ziyue K., Tran, Chau P., Wang, Chung, Guan, Johnny, Wu, Anna M., Reiter, Robert E. |
author_facet | Zhang, Mo, Kobayashi, Naoko, Zettlitz, Kirstin A., Kono, Evelyn A., Yamashiro, Joyce M., Tsai, Wen-Ting K., Jiang, Ziyue K., Tran, Chau P., Wang, Chung, Guan, Johnny, Wu, Anna M., Reiter, Robert E., Zhang, Mo, Kobayashi, Naoko, Zettlitz, Kirstin A., Kono, Evelyn A., Yamashiro, Joyce M., Tsai, Wen-Ting K., Jiang, Ziyue K., Tran, Chau P., Wang, Chung, Guan, Johnny, Wu, Anna M., Reiter, Robert E. |
author_sort | zhang, mo |
container_issue | 1 |
container_start_page | 188 |
container_title | Clinical Cancer Research |
container_volume | 25 |
description | <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>The inability to intraoperatively distinguish primary tumor, as well as lymphatic spread, increases the probability of positive surgical margins, tumor recurrence, and surgical toxicity. The goal of this study was to develop a tumor-specific optical probe for real-time fluorescence-guided surgery.</jats:p> </jats:sec> <jats:sec> <jats:title>Experimental Design:</jats:title> <jats:p>A humanized antibody fragment against PSCA (A11 minibody, A11 Mb) was conjugated with a near-infrared fluorophore, IRDye800CW. The integrity and binding of the probe to PSCA were confirmed by gel electrophoresis, size-exclusion chromatography, and flow cytometry, respectively. The ability of the probe to detect tumor-infiltrated lymph nodes and metastatic lesions was evaluated in 2 xenograft models, as well as in transgenic mice expressing human PSCA (hPSCA). An invasive intramuscular model was utilized to evaluate the efficacy of the A11 Mb-IRDye800CW-guided surgery.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>A11 Mb was successfully conjugated with IRDye800CW and retained specific binding to PSCA. In vivo imaging showed maximal signal-to-background ratios at 48 hours. The A11 Mb-IRDye800CW specifically detected PSCA-positive primary tumors, tumor-infiltrated lymph nodes, and distant metastases with high contrast. Fluorescence guidance facilitated more complete tumor resection, reduced tumor recurrence, and improved overall survival, compared with conventional white light surgery. The probe successfully identified primary orthotopic tumors and metastatic lesions in hPSCA transgenic mice.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Real-time fluorescence image–guided surgery with A11 Mb-IRDye800CW enabled detection of lymph node metastases and positive surgical margins, facilitated more complete tumor removal, and improved survival, compared with white light surgery. These results may be translatable into clinical practice to improve surgical and patient outcomes.</jats:p> </jats:sec> |
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imprint | American Association for Cancer Research (AACR), 2019 |
imprint_str_mv | American Association for Cancer Research (AACR), 2019 |
institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
issn | 1078-0432, 1557-3265 |
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match_str | zhang2019nearinfrareddyelabeledantiprostatestemcellantigenminibodyenablesrealtimefluorescenceimagingandtargetedsurgeryintranslationalmousemodels |
mega_collection | American Association for Cancer Research (AACR) (CrossRef) |
physical | 188-200 |
publishDate | 2019 |
publishDateSort | 2019 |
publisher | American Association for Cancer Research (AACR) |
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series | Clinical Cancer Research |
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spelling | Zhang, Mo Kobayashi, Naoko Zettlitz, Kirstin A. Kono, Evelyn A. Yamashiro, Joyce M. Tsai, Wen-Ting K. Jiang, Ziyue K. Tran, Chau P. Wang, Chung Guan, Johnny Wu, Anna M. Reiter, Robert E. 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-18-1382 <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>The inability to intraoperatively distinguish primary tumor, as well as lymphatic spread, increases the probability of positive surgical margins, tumor recurrence, and surgical toxicity. The goal of this study was to develop a tumor-specific optical probe for real-time fluorescence-guided surgery.</jats:p> </jats:sec> <jats:sec> <jats:title>Experimental Design:</jats:title> <jats:p>A humanized antibody fragment against PSCA (A11 minibody, A11 Mb) was conjugated with a near-infrared fluorophore, IRDye800CW. The integrity and binding of the probe to PSCA were confirmed by gel electrophoresis, size-exclusion chromatography, and flow cytometry, respectively. The ability of the probe to detect tumor-infiltrated lymph nodes and metastatic lesions was evaluated in 2 xenograft models, as well as in transgenic mice expressing human PSCA (hPSCA). An invasive intramuscular model was utilized to evaluate the efficacy of the A11 Mb-IRDye800CW-guided surgery.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>A11 Mb was successfully conjugated with IRDye800CW and retained specific binding to PSCA. In vivo imaging showed maximal signal-to-background ratios at 48 hours. The A11 Mb-IRDye800CW specifically detected PSCA-positive primary tumors, tumor-infiltrated lymph nodes, and distant metastases with high contrast. Fluorescence guidance facilitated more complete tumor resection, reduced tumor recurrence, and improved overall survival, compared with conventional white light surgery. The probe successfully identified primary orthotopic tumors and metastatic lesions in hPSCA transgenic mice.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Real-time fluorescence image–guided surgery with A11 Mb-IRDye800CW enabled detection of lymph node metastases and positive surgical margins, facilitated more complete tumor removal, and improved survival, compared with white light surgery. These results may be translatable into clinical practice to improve surgical and patient outcomes.</jats:p> </jats:sec> Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models Clinical Cancer Research |
spellingShingle | Zhang, Mo, Kobayashi, Naoko, Zettlitz, Kirstin A., Kono, Evelyn A., Yamashiro, Joyce M., Tsai, Wen-Ting K., Jiang, Ziyue K., Tran, Chau P., Wang, Chung, Guan, Johnny, Wu, Anna M., Reiter, Robert E., Clinical Cancer Research, Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models, Cancer Research, Oncology |
title | Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models |
title_full | Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models |
title_fullStr | Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models |
title_full_unstemmed | Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models |
title_short | Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models |
title_sort | near-infrared dye-labeled anti-prostate stem cell antigen minibody enables real-time fluorescence imaging and targeted surgery in translational mouse models |
title_unstemmed | Near-Infrared Dye-Labeled Anti-Prostate Stem Cell Antigen Minibody Enables Real-Time Fluorescence Imaging and Targeted Surgery in Translational Mouse Models |
topic | Cancer Research, Oncology |
url | http://dx.doi.org/10.1158/1078-0432.ccr-18-1382 |