Fluorescent Affibody Molecule Administered In Vivo at a Microdose Level Labels EGFR Expressing Glioma Tumor Regions

• Published in: Molecular imaging and biology Vol. 19; no. 1; pp. 41 - 48
• Main Authors: de Souza, Ana Luiza Ribeiro, Marra, Kayla, Gunn, Jason, Samkoe, Kimberley S., Hoopes, P. Jack, Feldwisch, Joachim, Paulsen, Keith D., Pogue, Brian W.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2017; Springer Nature B.V
• Subjects: Animals; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Line, Tumor; ErbB Receptors - metabolism; Female; Fluorescence; Glioma - metabolism; Glioma - pathology; Humans; Image Processing, Computer-Assisted; Imaging; Medicine; Medicine & Public Health; Radiology; Rats, Nude; Recombinant Fusion Proteins - administration & dosage; Research Article; Signal Processing, Computer-Assisted; Staining and Labeling; fluorescence-guided surgery; Glioma; Anti-EGFR affibody molecule; Pre-GMP ABY-029
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-016-0980-7

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.