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- Title
Fluorescent Affibody Molecule Administered In Vivo at a Microdose Level Labels EGFR Expressing Glioma Tumor Regions.
- Authors
Souza, Ana; Marra, Kayla; Gunn, Jason; Samkoe, Kimberley; Hoopes, P.; Feldwisch, Joachim; Paulsen, Keith; Pogue, Brian; de Souza, Ana Luiza Ribeiro; Samkoe, Kimberley S; Hoopes, P Jack; Paulsen, Keith D; Pogue, Brian W
- Abstract
<bold>Purpose: </bold>Fluorescence guidance in surgical oncology provides the potential to realize enhanced molecular tumor contrast with dedicated targeted tracers, potentially with a microdose injection level. For most glioma tumors, the blood brain barrier is compromised allowing some exogenous drug/molecule delivery and accumulation for imaging. The aberrant overexpression and/or activation of epidermal growth factor receptor (EGFR) is associated with many types of cancers, including glioblastoma, and so the use of a near-infrared (NIR) fluorescent molecule targeted to the EGFR receptor provides the potential for improving tumor contrast during surgery. Fluorescently labeled affibody molecule (ABY-029) has high EGFR affinity and high potential specificity with reasonably fast plasma clearance. In this study, ABY-29 was evaluated in glioma versus normal brain uptake from intravenous injection at a range of doses, down to a microdose injection level.<bold>Procedure: </bold>Nude rats were inoculated with the U251 human glioma cell line in the brain. Tumors were allowed to grow for 3-4 weeks. ABY-029 fluorescence ex vivo imaging of brain slices was acquired at different time points (1-48 h) and varying injection doses from 25 to 122 μg/kg (from human protein microdose equivalent to five times microdose levels).<bold>Results: </bold>The tumor was most clearly visualized at 1-h post-injection with 8- to 16-fold average contrast relative to normal brain. However, the tumor still could be identified after 48 h. In all cases, the ABY-029 fluorescence appeared to localize preferentially in EGFR-positive regions. Increasing the injected dose from a microdose level to five times, a microdose level increased the signal by 10-fold, and the contrast was from 8 to 16, showing that there was value in doses slightly higher than the microdose restriction. Normal tissue uptake was found to be affected by the tumor size, indicating that edema was a likely factor affecting the expected tumor to normal tissue contrast.<bold>Conclusion: </bold>These results suggest that the NIR-labeled affibody molecules provide an excellent potential to increase surgical visualization of EGFR-positive tumor regions.
- Subjects
GLIOMA treatment; EPIDERMAL growth factor receptors regulation; NERVOUS system tumors; IN vivo studies; GLIOBLASTOMA multiforme treatment; FLUORESCENT probes; ANIMAL experimentation; BRAIN tumors; CELL lines; EPIDERMAL growth factor; GLIOMAS; DIGITAL image processing; LIGHT; RATS; RECOMBINANT proteins; RESEARCH funding; SIGNAL processing; STAINS &; staining (Microscopy)
- Publication
Molecular Imaging & Biology, 2017, Vol 19, Issue 1, p41
- ISSN
1536-1632
- Publication type
journal article
- DOI
10.1007/s11307-016-0980-7