Towards Photodynamic Image-Guided Surgery of Head and Neck Tumors: Photodynamic Priming Improves Delivery and Diagnostic Accuracy of Cetuximab-IRDye800CW
Fluorescence image-guided surgery (IGS) using antibody conjugates of the fluorophore IRDye800CW have revolutionized the surgical debulking of tumors. Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, conjugated to IRDye800CW (Cet-IRDye800) is the first molecular targete...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.853660/full |
| _version_ | 1811237033462464512 |
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| author | Chanda Bhandari John Fakhry Menitte Eroy Jane Junghwa Song Kimberley Samkoe Tayyaba Hasan Tayyaba Hasan Kenneth Hoyt Girgis Obaid |
| author_facet | Chanda Bhandari John Fakhry Menitte Eroy Jane Junghwa Song Kimberley Samkoe Tayyaba Hasan Tayyaba Hasan Kenneth Hoyt Girgis Obaid |
| author_sort | Chanda Bhandari |
| collection | DOAJ |
| description | Fluorescence image-guided surgery (IGS) using antibody conjugates of the fluorophore IRDye800CW have revolutionized the surgical debulking of tumors. Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, conjugated to IRDye800CW (Cet-IRDye800) is the first molecular targeted antibody probe to be used for IGS in head and neck cancer patients. In addition to surgical debulking, Cetuximab-targeted photodynamic therapy (photoimmunotherapy; PIT) is emerging in the clinic as a powerful modality for head and neck tumor photodestruction. A plethora of other photoactivable agents are also in clinical trials for photodynamic-based therapies of head and neck cancer. Considering the vascular and stromal modulating effects of sub-therapeutic photodynamic therapy, namely photodynamic priming (PDP), this study explores the potential synergy between PDP and IGS for a novel photodynamic image-guided surgery (P-IGS) strategy. To the best of our knowledge, this is the first demonstration that PDP of the tumor microenvironment can augment the tumor delivery of full-length antibodies, namely Cet-IRDye800. In this study, we demonstrate a proof-of-concept that PDP primes orthotopic FaDu human head and neck tumors in mice for P-IGS by increasing the delivery of Cet-IRDye800 by up to 138.6%, by expediting its interstitial accumulation by 10.5-fold, and by increasing its fractional tumor coverage by 49.5% at 1 h following Cet-IRDye800 administration. Importantly, PDP improves the diagnostic accuracy of tumor detection by up to 264.2% with respect to vicinal salivary glands at 1 h. As such, PDP provides a time-to-surgery benefit by reducing the time to plateau 10-fold from 25.7 h to 2.5 h. We therefore propose that a pre-operative PDP regimen can expedite and augment the accuracy of IGS-mediated surgical debulking of head and neck tumors and reduce the time-to-IGS. Furthermore, this P-IGS regimen, can also enable a forward-looking post-operative protocol for the photodestruction of unresectable microscopic disease in the surgical bed. Beyond this scope, the role of PDP in the homogenous delivery of diagnostic, theranostic and therapeutic antibodies in solid tumors is of considerable significance to the wider community. |
| first_indexed | 2024-04-12T12:18:42Z |
| format | Article |
| id | doaj.art-3f8234b1c7cf4b5b93f65c7332661e5e |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T12:18:42Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3f8234b1c7cf4b5b93f65c7332661e5e2022-12-22T03:33:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.853660853660Towards Photodynamic Image-Guided Surgery of Head and Neck Tumors: Photodynamic Priming Improves Delivery and Diagnostic Accuracy of Cetuximab-IRDye800CWChanda Bhandari0John Fakhry1Menitte Eroy2Jane Junghwa Song3Kimberley Samkoe4Tayyaba Hasan5Tayyaba Hasan6Kenneth Hoyt7Girgis Obaid8Department of Bioengineering, University of Texas at Dallas, Richardson, TX, United StatesDepartment of Bioengineering, University of Texas at Dallas, Richardson, TX, United StatesDepartment of Bioengineering, University of Texas at Dallas, Richardson, TX, United StatesDepartment of Bioengineering, University of Texas at Dallas, Richardson, TX, United StatesThayer School of Engineering, Dartmouth College, Hanover, NH, United StatesWellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesDivision of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA, United StatesDepartment of Bioengineering, University of Texas at Dallas, Richardson, TX, United StatesDepartment of Bioengineering, University of Texas at Dallas, Richardson, TX, United StatesFluorescence image-guided surgery (IGS) using antibody conjugates of the fluorophore IRDye800CW have revolutionized the surgical debulking of tumors. Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, conjugated to IRDye800CW (Cet-IRDye800) is the first molecular targeted antibody probe to be used for IGS in head and neck cancer patients. In addition to surgical debulking, Cetuximab-targeted photodynamic therapy (photoimmunotherapy; PIT) is emerging in the clinic as a powerful modality for head and neck tumor photodestruction. A plethora of other photoactivable agents are also in clinical trials for photodynamic-based therapies of head and neck cancer. Considering the vascular and stromal modulating effects of sub-therapeutic photodynamic therapy, namely photodynamic priming (PDP), this study explores the potential synergy between PDP and IGS for a novel photodynamic image-guided surgery (P-IGS) strategy. To the best of our knowledge, this is the first demonstration that PDP of the tumor microenvironment can augment the tumor delivery of full-length antibodies, namely Cet-IRDye800. In this study, we demonstrate a proof-of-concept that PDP primes orthotopic FaDu human head and neck tumors in mice for P-IGS by increasing the delivery of Cet-IRDye800 by up to 138.6%, by expediting its interstitial accumulation by 10.5-fold, and by increasing its fractional tumor coverage by 49.5% at 1 h following Cet-IRDye800 administration. Importantly, PDP improves the diagnostic accuracy of tumor detection by up to 264.2% with respect to vicinal salivary glands at 1 h. As such, PDP provides a time-to-surgery benefit by reducing the time to plateau 10-fold from 25.7 h to 2.5 h. We therefore propose that a pre-operative PDP regimen can expedite and augment the accuracy of IGS-mediated surgical debulking of head and neck tumors and reduce the time-to-IGS. Furthermore, this P-IGS regimen, can also enable a forward-looking post-operative protocol for the photodestruction of unresectable microscopic disease in the surgical bed. Beyond this scope, the role of PDP in the homogenous delivery of diagnostic, theranostic and therapeutic antibodies in solid tumors is of considerable significance to the wider community.https://www.frontiersin.org/articles/10.3389/fonc.2022.853660/fullIGSphotodynamic priminghead and neck cancermonoclonal antibodiesNIR fluorophorestumor delivery |
| spellingShingle | Chanda Bhandari John Fakhry Menitte Eroy Jane Junghwa Song Kimberley Samkoe Tayyaba Hasan Tayyaba Hasan Kenneth Hoyt Girgis Obaid Towards Photodynamic Image-Guided Surgery of Head and Neck Tumors: Photodynamic Priming Improves Delivery and Diagnostic Accuracy of Cetuximab-IRDye800CW Frontiers in Oncology IGS photodynamic priming head and neck cancer monoclonal antibodies NIR fluorophores tumor delivery |
| title | Towards Photodynamic Image-Guided Surgery of Head and Neck Tumors: Photodynamic Priming Improves Delivery and Diagnostic Accuracy of Cetuximab-IRDye800CW |
| title_full | Towards Photodynamic Image-Guided Surgery of Head and Neck Tumors: Photodynamic Priming Improves Delivery and Diagnostic Accuracy of Cetuximab-IRDye800CW |
| title_fullStr | Towards Photodynamic Image-Guided Surgery of Head and Neck Tumors: Photodynamic Priming Improves Delivery and Diagnostic Accuracy of Cetuximab-IRDye800CW |
| title_full_unstemmed | Towards Photodynamic Image-Guided Surgery of Head and Neck Tumors: Photodynamic Priming Improves Delivery and Diagnostic Accuracy of Cetuximab-IRDye800CW |
| title_short | Towards Photodynamic Image-Guided Surgery of Head and Neck Tumors: Photodynamic Priming Improves Delivery and Diagnostic Accuracy of Cetuximab-IRDye800CW |
| title_sort | towards photodynamic image guided surgery of head and neck tumors photodynamic priming improves delivery and diagnostic accuracy of cetuximab irdye800cw |
| topic | IGS photodynamic priming head and neck cancer monoclonal antibodies NIR fluorophores tumor delivery |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.853660/full |
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