Title

Novel DNA Polymer for Amplification Pretargeting

UMMS Affiliation

Department of Radiology

Date

7-27-2015

Document Type

Article

Disciplines

Medicinal-Pharmaceutical Chemistry | Radiology

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.

Rights and Permissions

Citation: ACS Med Chem Lett. 2015 Jul 27;6(9):972-6. eCollection 2015 Sep 10. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Keywords

99mTc, DNA polymer, amplification, pretargeting

PubMed ID

26396682