Abstract
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Objectives Triple Negative Breast Cancer (TNBC) represents a group of refractory breast cancer with aggressive clinical manifestations as well as poor prognosis. Epidermal growth factor receptor (EGFR) expression is strongly associated with TNBC progression and it may serve as a therapeutic target for TNBC. We aimed to use EGFR Affibody based PET imaging to profile EGFR expression and to evaluate the response from anti-EGFR treatment in TNBC tumor bearing mice.
Methods Ac-Cys-ZEGFR:1907 was chemically synthesized using a solid phase peptide synthesizer and then site-specifically conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for radiolabeling or N-2-(4-18F-fluorobenzamido)-ethyl]-maleimide (18F-FBEM). The in vitro cell uptake study was performed using TNBC SUM159 cells. The biodistribution and microPET imaging using 64Cu-DOTA-ZEGFR:1907 or 18F-FBEM- ZEGFR:1907 were evaluated in nude mice bearing subcutaneous SUM159 tumors.
Results Ac-Cys-ZEGFR:1907 was successfully synthesized and radiolabeled with 64Cu. Biodistribution study showed that tumor uptake value of 64Cu-Ac-Cys-ZEGFR:1907 remained at 4.07 ± 0.93 %ID/g at 24 h in nude mice (n = 4) bearing SUM159 xenografts. Furthermore, microPET imaging study demonstrated that 64Cu-DOTA-Ac-Cys-ZEGFR:1907 and 18F-FBEM- ZEGFR:1907 could both specifically delineate the EGFR positive TNBC tumor in vivo (Figure).
Conclusions The study successfully demonstrated that 64Cu-DOTA-Ac-Cys-ZEGFR:1907 and 18F-FBEM- ZEGFR:1907 are promising molecular probes for PET imaging of EGFR expression in TNBC. The anti-EGFR targeted therapy is currently undergoing in TNBC models and EGFR targeted imaging will be utilized for profiling the EGFR as an effective TNBC biomarker