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Miller J , Doss M , McQuillen R , Shaller CC , Tolner B , Yu JQ , Chester K , Robinson MK
Impact of expression system on the function of the C6.5 diabody PET radiotracer
Tumor Biology. 2012 Jun;33(3) :617-627
AbstractThe ability of engineered antibodies to rapidly and selectively target tumors that express their target antigen makes them well suited for use as radioimaging tracers. The combination of molecular size and bivalent nature makes diabody molecules a particularly promising structure for use as radiotracers for diagnostic imaging. Previous data have demonstrated that the anti-HER2 C6.5 diabody (C6.5db) is an effective radiotracer in preclinical models of HER2-positive cancer. The aim of this study was to evaluate the impact on radiotracer performance, associated with expressing the C6.5db in the Pichia pastoris (P-C6.5db) system as compared to Escherichia coli (E. C6.5db). Glycosylation of P-C6.5db led to faster blood clearance and lower overall tumor uptake than seen with E. coli-produced C6.5db. However, P-C6.5db achieved high tumor/background ratios that are critical for effective imaging. Dosimetry measurements determined in this study for both I-124-P-C6.5db and I-124-E-C6.5db suggest that they are equivalent to other radiotracers currently being administered to patients.
NotesMiller, Joshua Doss, Mohan McQuillen, Ryan Shaller, Calvin C. Tolner, Berend Yu, Jian Q. Chester, Kerry Robinson, Matthew K. HRSA; Commonwealth of Pennsylvania; Breast Cancer Campaign, UK This work was supported in part by a HRSA grant to the American Russian Cancer Alliance and through support by an appropriation from the Commonwealth of Pennsylvania. Part of this work was supported by The Breast Cancer Campaign, UK. We thank G. Adams for scientific discussions. We acknowledge the Laboratory Animal Facility and the Instrument Shop at the Fox Chase Cancer Center for their expert technical assistance. 49 Springer Dordrecht Si 935pa