Microscale receiver operating characteristic analysis of micrometastasis recognition using activatable fluorescent probes indicates leukocyte imaging as a critical factor to enhance accuracy
Molecular-targeted probes are emerging with applications for optical biopsy of cancer. An underexplored potential clinical use of these probes is to monitor residual cancer micrometastases that escape cytoreductive surgery and chemotherapy. Here, we show that leukocytes, or white blood cells, residi...
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2014
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Online Access: | http://hdl.handle.net/1721.1/91179 |
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author | Spring, Bryan Q. Palanisami, Akilan Hasan, Tayyaba |
author2 | Harvard University--MIT Division of Health Sciences and Technology |
author_facet | Harvard University--MIT Division of Health Sciences and Technology Spring, Bryan Q. Palanisami, Akilan Hasan, Tayyaba |
author_sort | Spring, Bryan Q. |
collection | MIT |
description | Molecular-targeted probes are emerging with applications for optical biopsy of cancer. An underexplored potential clinical use of these probes is to monitor residual cancer micrometastases that escape cytoreductive surgery and chemotherapy. Here, we show that leukocytes, or white blood cells, residing in nontumor tissues—as well as those infiltrating micrometastatic lesions—uptake cancer cell-targeted, activatable immunoconjugates nonspecifically, which limits the accuracy and resolution of micrometastasis recognition using these probes. Receiver operating characteristic analysis of freshly excised tissues from a mouse model of peritoneal carcinomatosis suggests that dual-color imaging, adding an immunostain for leukocytes, offers promise for enabling accurate recognition of single cancer cells. Our results indicate that leukocyte identification improves micrometastasis recognition sensitivity and specificity from 92 to 93%—for multicellular metastases >20 to 30 μm in size—to 98 to 99.9% for resolving metastases as small as a single cell. |
first_indexed | 2024-09-23T09:05:10Z |
format | Article |
id | mit-1721.1/91179 |
institution | Massachusetts Institute of Technology |
language | en_US |
last_indexed | 2024-09-23T09:05:10Z |
publishDate | 2014 |
publisher | SPIE |
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spelling | mit-1721.1/911792022-09-26T10:17:47Z Microscale receiver operating characteristic analysis of micrometastasis recognition using activatable fluorescent probes indicates leukocyte imaging as a critical factor to enhance accuracy Spring, Bryan Q. Palanisami, Akilan Hasan, Tayyaba Harvard University--MIT Division of Health Sciences and Technology Hasan, Tayyaba Molecular-targeted probes are emerging with applications for optical biopsy of cancer. An underexplored potential clinical use of these probes is to monitor residual cancer micrometastases that escape cytoreductive surgery and chemotherapy. Here, we show that leukocytes, or white blood cells, residing in nontumor tissues—as well as those infiltrating micrometastatic lesions—uptake cancer cell-targeted, activatable immunoconjugates nonspecifically, which limits the accuracy and resolution of micrometastasis recognition using these probes. Receiver operating characteristic analysis of freshly excised tissues from a mouse model of peritoneal carcinomatosis suggests that dual-color imaging, adding an immunostain for leukocytes, offers promise for enabling accurate recognition of single cancer cells. Our results indicate that leukocyte identification improves micrometastasis recognition sensitivity and specificity from 92 to 93%—for multicellular metastases >20 to 30 μm in size—to 98 to 99.9% for resolving metastases as small as a single cell. National Institutes of Health (U.S.) (Grant R01-AR40352) National Institutes of Health (U.S.) (Grant RC1-CA146337) National Institutes of Health (U.S.) (Grant R01-CA160998) National Institutes of Health (U.S.) (Grant P01-CA084203) 2014-10-27T15:03:38Z 2014-10-27T15:03:38Z 2014-06 2014-04 Article http://purl.org/eprint/type/JournalArticle 1083-3668 1560-2281 http://hdl.handle.net/1721.1/91179 Spring, Bryan Q., Akilan Palanisami, and Tayyaba Hasan. “Microscale Receiver Operating Characteristic Analysis of Micrometastasis Recognition Using Activatable Fluorescent Probes Indicates Leukocyte Imaging as a Critical Factor to Enhance Accuracy.” Journal of Biomedical Optics 19, no. 6 (June 1, 2014): 066006. © 2014 Society of Photo-Optical Instrumentation Engineers en_US http://dx.doi.org/10.1117/1.JBO.19.6.066006 Journal of Biomedical Optics Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf SPIE SPIE |
spellingShingle | Spring, Bryan Q. Palanisami, Akilan Hasan, Tayyaba Microscale receiver operating characteristic analysis of micrometastasis recognition using activatable fluorescent probes indicates leukocyte imaging as a critical factor to enhance accuracy |
title | Microscale receiver operating characteristic analysis of micrometastasis recognition using activatable fluorescent probes indicates leukocyte imaging as a critical factor to enhance accuracy |
title_full | Microscale receiver operating characteristic analysis of micrometastasis recognition using activatable fluorescent probes indicates leukocyte imaging as a critical factor to enhance accuracy |
title_fullStr | Microscale receiver operating characteristic analysis of micrometastasis recognition using activatable fluorescent probes indicates leukocyte imaging as a critical factor to enhance accuracy |
title_full_unstemmed | Microscale receiver operating characteristic analysis of micrometastasis recognition using activatable fluorescent probes indicates leukocyte imaging as a critical factor to enhance accuracy |
title_short | Microscale receiver operating characteristic analysis of micrometastasis recognition using activatable fluorescent probes indicates leukocyte imaging as a critical factor to enhance accuracy |
title_sort | microscale receiver operating characteristic analysis of micrometastasis recognition using activatable fluorescent probes indicates leukocyte imaging as a critical factor to enhance accuracy |
url | http://hdl.handle.net/1721.1/91179 |
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