title: Impact of expression system on the function of the C6.5 diabody PET radiotracer.
abstract: The 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 (124)I-P-C6.5db and (124)I-E-C6.5db suggest that they are equivalent to other radiotracers currently being administered to patients.
authors.affiliation: Developmental Therapeutics Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Miller
authors.forename: Mohan
authors.initials: M
authors.lastname: Doss
authors.forename: Ryan
authors.initials: R
authors.lastname: McQuillen
authors.forename: Calvin C
authors.initials: CC
authors.lastname: Shaller
authors.forename: Berend
authors.initials: B
authors.lastname: Tolner
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Yu
authors.forename: Kerry
authors.initials: K
authors.lastname: Chester
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Robinson
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D016513:Mice, SCID; D064847:Multimodal Imaging; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000493:pharmacokinetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000235:genetics / Q000493:pharmacokinetics; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014183:Transplantation, Heterologous; D015003:Yeasts / Q000378:metabolism
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D057127:Single-Chain Antibodies