Synthesis and Feasibility Evaluation of a new Trastuzumab Conjugate Integrated with Paclitaxel and 89Zr for Theranostic Application Against HER2-Expressing Breast Cancers

Joo Hee Jang; Sang Jin Han; Jung Young Kim; Kwang Il Kim; Kyo Chul Lee; Chi Soo Kang

doi:10.1002/open.201900037

Synthesis and Feasibility Evaluation of a new Trastuzumab Conjugate Integrated with Paclitaxel and ⁸⁹Zr for Theranostic Application Against HER2-Expressing Breast Cancers

ChemistryOpen. 2019 Apr 8;8(4):451-456. doi: 10.1002/open.201900037. eCollection 2019 Apr.

Authors

Joo Hee Jang¹, Sang Jin Han¹, Jung Young Kim¹, Kwang Il Kim¹, Kyo Chul Lee¹, Chi Soo Kang¹

Affiliation

¹ Division of Applied RI Korea Institute of Radiological and Medical Sciences 75 Nowon-ro, Nowon-gu Seoul Korea 01812.

Abstract

The preparation and in vitro evaluation of a theranostic conjugate composed of trastuzumab, paclitaxel (PTX), and deferoxamine (DFO)-chelated ⁸⁹Zr have been reported. These comounds have potential applications against HER2 receptor positive breast cancers. We conjugated DFO and PTX to trastuzumab by exploiting simple conjugation chemistry. The conjugate (DFO-trastuzumab-PTX) showed excellent radiolabeling efficiency with ⁸⁹Zr and the labeled conjugate had high in vitro stability in human serum. Furthermore, DFO-trastuzumab-PTX displayed comparable cytotoxicity with PTX and ⁸⁹Zr-DFO-trastuzumab-PTX exhibited HER2 receptor-mediated binding on HER2-positive MDA-MB-231 breast cancer cells. The results of our in vitro study indicate high potential of ⁸⁹Zr-DFO-trastuzumab-PTX to be utilized in the theranostic application against HER2-postive breast cancers.

Keywords: 89Zr; breast cancer; paclitaxel; theranostics; trastuzumab.