title: Rapid visualization of human tumor xenografts through optical imaging with a near-infrared fluorescent anti-epidermal growth factor receptor nanobody.
abstract: Given that overexpression of the epidermal growth factor receptor (EGFR) is found in many types of human epithelial cancers, noninvasive molecular imaging of this receptor is of great interest. A number of studies have employed monoclonal antibodies as probes; however, their characteristic long half-life in the bloodstream has encouraged the development of smaller probes. In this study, an anti-EGFR nanobody-based probe was developed and tested in comparison with cetuximab for application in optical molecular imaging. To this aim, the anti-EGFR nanobody 7D12 and cetuximab were conjugated to the near-infrared fluorophore IRDye800CW. 7D12-IR allowed the visualization of tumors as early as 30 minutes postinjection, whereas with cetuximab-IR, no signal above background was observed at the tumor site. Quantification of the IR-conjugated proteins in the tumors revealed ≈ 17% of injected dose per gram 2 hours after injection of 7D12-IR, which was significantly higher than the tumor uptake obtained 24 hours after injection of cetuximab-IR. This difference is associated with the superior penetration and distribution of 7D12-IR within the tumor. These results demonstrate that this anti-EGFR nanobody conjugated to the NIR fluorophore has excellent properties for rapid preclinical optical imaging, which holds promise for its future use as a complementary diagnostic tool in humans.
authors.affiliation: Department of Biology, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Oliveira
authors.forename: Guus A M S
authors.initials: GA
authors.lastname: van Dongen
authors.forename: Marijke
authors.initials: M
authors.lastname: Stigter-van Walsum
authors.forename: Rob C
authors.initials: RC
authors.lastname: Roovers
authors.forename: Jord C
authors.initials: JC
authors.lastname: Stam
authors.forename: Willem
authors.initials: W
authors.lastname: Mali
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Paul M P
authors.initials: PM
authors.lastname: van Bergen en Henegouwen
mesh_terms: D000818:Animals; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D066246:ErbB Receptors