A Novel Bimodal Imaging Agent Targeting HER2 Molecule of Breast Cancer.

Wei Lv,Lijun Yuan,Li Zhang,Rui Yang,Hengli Yang,Jian Zhang,Wenbin Cai,Yunyou Duan,Yamei Shen

doi:10.1155/2018/6202876

Abstract

Nanobubble (NB), a newly developed nanoscaled ultrasound contrast agent (UCA) for molecular imaging, has been widely researched for these years. Targeting it with functional molecule, nanobubble can adhere selectively to cellular epitopes and receptors outside the vasculature via enhanced permeability and retention (EPR) effect of tumor blood vessel. To enhance the targeting rate of our previous prepared NBs-Affibody for HER2 (+) breast cancer imaging, we introduced a near-infrared fluorescent (NIRF) dye, IR783, in this study to enhance tumor-specific targeting rate and provide a promising modality for dual-mode imaging. The prepared IR783-NBs-Affibody presented a uniform nanoscale size around 482.7 ± 54.3 nm, good biosecurity, and stability over time. The encapsulation efficiency (EE) of IR-783 was 15.09% in the conjugates leading to a successful NIR fluorescence and ultrasound enhancement imaging ex vivo. IR783-NBs-Affibody was able to automatically accumulate on BT474 cells with a highly increased targeting rate of 85.4% compared with previous NBs-Affibody of 26.6%, while Affibody-guided HER2 binding was only found in HER2-positive cell lines (BT474 and T-47D). The newly developed IR783-NBs-Affibody is characterized with favorable HER2 targeting ability and bimodal imaging capability for breast cancer. Thus, IR783-NBs-Affibody holds great potential in molecular diagnosis for patients with breast cancer.

Highlights

The overexpressed HER2 receptor is a valuable biomarker for breast cancer as it accounts for about 15–20% for those patients who have been diagnosed with breast cancer
Considering a limited targeting rate around 20% and a comparatively poor axillary lymph nodes (ALNs) imaging capability for ultrasound contrast agent (UCA), in this study, we introduced another near-infra fluorescent dye as we tried previously [9], IR783, which has been approved for a tumor-targeting selectivity and enhanced new bubbles’ targeting rate as well as a higher sensitivity for sentinel lymph node (SLN) mapping due to their low background autofluorescence
IR783-NBs-Affibody and SonoVue microbubbles obviously appeared spherical under TEM scanning

Summary

Introduction

The overexpressed HER2 receptor is a valuable biomarker for breast cancer as it accounts for about 15–20% for those patients who have been diagnosed with breast cancer. It is the only one that has improved the clinical management for patients with HER2 (+) by using anti-HER2 targeted agents, such as trastuzumab, lapatinib, and pertuzumab [1]. According to the published joint guideline recommendations in 2007 of the College of American Pathologists (CAP) and the American Society of Clinical Oncology (ASCO), it has been a routine pathological diagnosis to detect HER2 status in breast cancer all over the world [3, 4], for the prognostic evaluation for breast cancer patients and a key element of the adjuvant therapy for HER2-. A more convictive method for comprehensive assessment of HER2 status of breast cancer is needed

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Discussion

Conclusion