Fluorescent Affibody Molecule Administered In Vivo at a Microdose Level Labels EGFR Expressing Glioma Tumor Regions
Purpose 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 d...
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Published in | Molecular imaging and biology Vol. 19; no. 1; pp. 41 - 48 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.02.2017
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Purpose
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.
Procedure
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).
Results
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.
Conclusion
These results suggest that the NIR-labeled affibody molecules provide an excellent potential to increase surgical visualization of EGFR-positive tumor regions. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1536-1632 1860-2002 |
DOI: | 10.1007/s11307-016-0980-7 |