Premium
Optimizing Glioma Detection Using an EGFR‐Targeted Fluorescent Affibody
Author(s) -
Ribeiro de Souza Ana Luiza,
Marra Kayla,
Gunn Jason,
Samkoe Kimberley S.,
Hull Sally,
Paulsen Keith D.,
Pogue Brian W.
Publication year - 2018
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.13003
Subject(s) - microdose , cetuximab , glioma , medicine , cancer research , nuclear medicine , cancer , colorectal cancer
Since many types of cancers overexpress EGFR , this surface receptor has been used as a target for therapy or diagnosis of malignant disease. Uptake kinetics of EGFR ‐targeted fluorescent Affibody ( ABY ‐029) were studied with a view toward optimizing efficacy of tumor detection in a glioma as a function of both delivered dose and concurrent administration of unlabeled cetuximab (an EGFR antagonist). U251 glioma cells were inoculated in brain of nude rats, and the fluorescence from each brain was analyzed after the administration of ABY ‐029. Although cetuximab was able to systematically block ABY ‐029 binding to EGFR in a dose‐dependent manner in cell culture, no influence on the tumor‐to‐normal brain contrast was seen when unlabeled cetuximab was administered prior to ABY ‐029. Ex vivo imaging of ABY ‐029 fluorescence showed increasing values of the tumor‐to‐normal brain ratio with an increasing injected dose. A saturation value was obtained at a dose of 245 μg kg −1 which represents a 10‐fold increase over a “microdose” value. According to FDA , the microdose of protein products is considered ≤30 nanomoles due to its difference in molecular weight as compared to synthetic drugs. This observation indicates that glioma detection will be optimal if the ABY ‐029 dose exceeds the “microdose” value.