Abstract
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.
Original language | English |
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Article number | e0147428 |
Journal | PloS one |
Volume | 11 |
Issue number | 2 |
Number of pages | 15 |
ISSN | 1932-6203 |
DOIs | |
Publication status | Published - 2016 |
Keywords
- Animals
- Cell Line, Tumor
- Diagnostic Imaging
- Dipeptides
- Enzyme-Linked Immunosorbent Assay
- Female
- Fluorescent Dyes
- Humans
- Indocyanine Green
- Ligands
- Mice
- Mice, Nude
- Neoplasms
- Oligopeptides
- Optical Imaging
- Peptides
- Protein Stability
- Receptors, Urokinase Plasminogen Activator
- Journal Article