Molecular imaging application of radioiodinated anti-EGFR human Fab to EGFR-overexpressing tumor xenografts.
BACKGROUND
Suitable diagnostics could identify patients who might benefit from targeted therapies. Molecular imaging is a promising method estimating the expression of specific molecules in vivo, and the goal of this study was to evaluate a radioiodinated anti-epidermal growth factor receptor (EGFR) human Fab as a molecular imaging agent for diagnosis.


METHODS
Three human tumor cell lines representing tumors with different levels of EGFR expression were selected and their corresponding xenografts produced. (125)I was conjugated to a human anti-EGFR Fab that recognizes the native extracellular domain of EGFR evidenced by immunoprecipitation (IP) and fluorescence-activated cell sorting (FACS) assays. Single-photon-emission computed tomography (SPECT) imaging of (125)I-Fab being administered to nude mice bearing xenografts were obtained, and further analyzed by region of interest (ROI) assay.


RESULTS
The (125)I-Fab was achieved successfully without losing its immunoreactivity. The scintigrams as well as ROI assay showed that (125)I-Fab was able to clearly quantitatively distinguish the different expression levels of EGFR in vivo.


CONCLUSIONS
(125)I-Fab is a potential molecular imaging agent for clinical diagnosis of EGFR-overexpressing tumors.
Cancer Center, Key Laboratory of Antibody Technology of Ministry of Health, Nanjing Medical University, Nanjing, Jiangsu 210029, PR China.
Ning
N
Xu
Gangming
G
Cai
Wanzhong
W
Ye
Xin
X
Wang
Yunqian
Y
Li
Ping
P
Zhao
Aixia
A
Zhang
Rongjun
R
Zhang
Brian
B
Cao
D000818:Animals; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry; D007128:Immunoglobulin Fragments / Q000737:chemistry / Q000276:immunology*; D047468:Immunoprecipitation; D007457:Iodine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D015899:Tomography, Emission-Computed, Single-Photon; D014183:Transplantation, Heterologous
D018796:Immunoconjugates; D007128:Immunoglobulin Fragments; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D066246:ErbB Receptors