Peptide-Based Optical uPAR Imaging for Surgery: In Vivo Testing of ICG-Glu-Glu-AE105.
Near infrared intra-operative optical imaging is an emerging technique with clear implications for improved cancer surgery by enabling a more distinct delineation of the tumor margins during resection. This modality has the potential to increase the number of patients having a curative radical tumor...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4734687?pdf=render |
| _version_ | 1818318736400056320 |
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| author | Karina Juhl Anders Christensen Morten Persson Michael Ploug Andreas Kjaer |
| author_facet | Karina Juhl Anders Christensen Morten Persson Michael Ploug Andreas Kjaer |
| author_sort | Karina Juhl |
| collection | DOAJ |
| description | Near infrared intra-operative optical imaging is an emerging technique with clear implications for improved cancer surgery by enabling a more distinct delineation of the tumor margins during resection. This modality has the potential to increase the number of patients having a curative radical tumor resection. In the present study, a new uPAR-targeted fluorescent probe was developed and the in vivo applicability was evaluated in a human xenograft mouse model. Most human carcinomas express high level of uPAR in the tumor-stromal interface of invasive lesions and uPAR is therefore considered an ideal target for intra-operative imaging. Conjugation of the flourophor indocyanine green (ICG) to the uPAR agonist (AE105) provides an optical imaging ligand with sufficiently high receptor affinity to allow for a specific receptor targeting in vivo. For in vivo testing, human glioblastoma xenograft mice were subjected to optical imaging after i.v. injection of ICG-AE105, which provided an optimal contrast in the time window 6-24 h post injection. Specificity of the uPAR-targeting probe ICG-AE105 was demonstrated in vivo by 1) no uptake of unconjugated ICG after 15 hours, 2) inhibition of ICG-AE105 tumor uptake by a bolus injection of the natural uPAR ligand pro-uPA, and finally 3) the histological colocalization of ICG-AE105 fluorescence and immunohistochemical detected human uPAR on resected tumor slides. Taken together, our data supports the potential use of this probe for intra-operative optical guidance in cancer surgery to ensure complete removal of tumors while preserving adjacent, healthy tissue. |
| first_indexed | 2024-12-13T09:57:57Z |
| format | Article |
| id | doaj.art-7225a4f9bd1e4206bbfa05fbcdbcbab9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T09:57:57Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7225a4f9bd1e4206bbfa05fbcdbcbab92022-12-21T23:51:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014742810.1371/journal.pone.0147428Peptide-Based Optical uPAR Imaging for Surgery: In Vivo Testing of ICG-Glu-Glu-AE105.Karina JuhlAnders ChristensenMorten PerssonMichael PlougAndreas KjaerNear infrared intra-operative optical imaging is an emerging technique with clear implications for improved cancer surgery by enabling a more distinct delineation of the tumor margins during resection. This modality has the potential to increase the number of patients having a curative radical tumor resection. In the present study, a new uPAR-targeted fluorescent probe was developed and the in vivo applicability was evaluated in a human xenograft mouse model. Most human carcinomas express high level of uPAR in the tumor-stromal interface of invasive lesions and uPAR is therefore considered an ideal target for intra-operative imaging. Conjugation of the flourophor indocyanine green (ICG) to the uPAR agonist (AE105) provides an optical imaging ligand with sufficiently high receptor affinity to allow for a specific receptor targeting in vivo. For in vivo testing, human glioblastoma xenograft mice were subjected to optical imaging after i.v. injection of ICG-AE105, which provided an optimal contrast in the time window 6-24 h post injection. Specificity of the uPAR-targeting probe ICG-AE105 was demonstrated in vivo by 1) no uptake of unconjugated ICG after 15 hours, 2) inhibition of ICG-AE105 tumor uptake by a bolus injection of the natural uPAR ligand pro-uPA, and finally 3) the histological colocalization of ICG-AE105 fluorescence and immunohistochemical detected human uPAR on resected tumor slides. Taken together, our data supports the potential use of this probe for intra-operative optical guidance in cancer surgery to ensure complete removal of tumors while preserving adjacent, healthy tissue.http://europepmc.org/articles/PMC4734687?pdf=render |
| spellingShingle | Karina Juhl Anders Christensen Morten Persson Michael Ploug Andreas Kjaer Peptide-Based Optical uPAR Imaging for Surgery: In Vivo Testing of ICG-Glu-Glu-AE105. PLoS ONE |
| title | Peptide-Based Optical uPAR Imaging for Surgery: In Vivo Testing of ICG-Glu-Glu-AE105. |
| title_full | Peptide-Based Optical uPAR Imaging for Surgery: In Vivo Testing of ICG-Glu-Glu-AE105. |
| title_fullStr | Peptide-Based Optical uPAR Imaging for Surgery: In Vivo Testing of ICG-Glu-Glu-AE105. |
| title_full_unstemmed | Peptide-Based Optical uPAR Imaging for Surgery: In Vivo Testing of ICG-Glu-Glu-AE105. |
| title_short | Peptide-Based Optical uPAR Imaging for Surgery: In Vivo Testing of ICG-Glu-Glu-AE105. |
| title_sort | peptide based optical upar imaging for surgery in vivo testing of icg glu glu ae105 |
| url | http://europepmc.org/articles/PMC4734687?pdf=render |
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