title: Novel DNA Polymer for Amplification Pretargeting.
abstract: In this Letter, different from conventional pretargeting, an additional novel DNA polymer with multiple copies of a target was first designed to be administrated between the antitumor antibody, and the labeled effector served as an amplification pretargeting strategy. Two phosphorothioate DNA strands, a bridging and a target strand, were hybridized to form a polymer. Polymer size, as a function of molar ratios, was then monitored by size exclusion HPLC and electrophoretic mobility shift assay. Moreover, binding efficiency of polymers with the radiolabeled effector and polymer size after hybridization were measured by HPLC as well. As the polymer was expected to produce more binding sites that would be targeted by effectors, amplification pretargeting can greatly improve accumulation of effectors in tumor. This novel proof-of-concept was then well demonstrated by the in vitro test of signal amplification in antibody-binding protein L coated plate and LS174T cells. Compared to conventional pretargeting, significantly increasing radioactive signal was observed in this designed amplification pretargeting, which would serve as a useful paradigm of the potential of oligomer polymers to improve pretargeting and other related approaches.
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University , Shanghai 200032, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine , Shanghai 200072, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University , Shanghai 200032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Nuclear Medicine, University of Massachusetts Medical School , Worcester, Massachusetts 01655, United States.
authors.forename: Guozheng
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, University of Massachusetts Medical School , Worcester, Massachusetts 01655, United States.
authors.forename: Shuping
authors.initials: S
authors.lastname: Dou
authors.affiliation: Department of Nuclear Medicine, University of Massachusetts Medical School , Worcester, Massachusetts 01655, United States.
authors.forename: Mary
authors.initials: M
authors.lastname: Rusckowski
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University , Shanghai 200032, China.
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Shi
authors.affiliation: Shanghai Institute of Applied Physics, Chinese Academy of Sciences , Shanghai 201800, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University , Shanghai 200032, China.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Cheng
keywords: 99mTc; DNA polymer; amplification; pretargeting