Diagnostic Value of ER, PR, FR and HER-2-Targeted Molecular Probes for Magnetic Resonance Imaging in Patients with Breast Cancer

Cell Physiol Biochem. 2018;49(1):271-281. doi: 10.1159/000492877. Epub 2018 Aug 23.

Abstract

Background/aims: Smart molecular probes are required in the application of Magnetic resonance imaging (MRI) for biochemical and clinical research. This study aims to investigate the diagnostic values of estrogen receptor (ER), progesterone receptor (PR), folate receptor (FR) and human epidermal growth factor receptor 2 (HER-2)-targeted molecular probes in the MRI diagnosis of breast cancer.

Methods: Initially, a total of 508 female breast cancer patients were selected for breast cancer subtype classification by immunohistochemistry. Subsequently, the tumor size, lymph node metastasis, and histological grade of different breast cancer subtypes were compared. Molecular probes of Ab-ER-USPIO, Ab-PR-USPIO, Ab-FR-USPIO and Ab-HER-2-USPIO were constructed and screened. The specific binding of molecular probes to breast cancer cells was detected both in vitro and in vivo by Prussian blue staining and MRI using T1 and T2 weighted images. Finally, in vivo toxicity of Ab-HER-2-USPIO was analyzed using hematoxylin and eosin staining.

Results: We identified the following subtypes of breast cancer: Luminal A (ER-positive, FR-positive, HER-2-negative), Luminal B (ER-positive, FR-positive, HER-2-positive), HER-2 overexpression (ER-negative, FR-negative, HER-2-positive), and triple-negative breast cancer (ER-negative, FR-negative, HER-2-negative). Featuring favorable in vitro biocompatibility and low in vivo toxicity, Ab-HER-2-USPIO can specifically bind to breast cancer cells BT47 and SKBR3, thus enhancing the quality of T1 weighted MRI images.

Conclusion: The results indicate that HER-2-targeted MRI molecular probes may be used in the clinical diagnosis of breast cancer and facilitate the development of promising strategies for breast cancer treatments.

Keywords: Breast cancer; Estrogen receptor; Folate receptor; Human epidermal growth factor receptor-2; Magnetic resonance imaging; Molecular probe; Progesterone receptor.

MeSH terms

  • Adult
  • Animals
  • Antibodies / chemistry
  • Antibodies / immunology
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Contrast Media / chemistry*
  • Dextrans / chemistry
  • Female
  • Folate Receptors, GPI-Anchored / chemistry
  • Folate Receptors, GPI-Anchored / metabolism*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Receptor, ErbB-2 / chemistry
  • Receptor, ErbB-2 / immunology
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / chemistry
  • Receptors, Progesterone / metabolism*

Substances

  • Antibodies
  • Contrast Media
  • Dextrans
  • Folate Receptors, GPI-Anchored
  • Magnetite Nanoparticles
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ferumoxtran-10
  • ERBB2 protein, human
  • Receptor, ErbB-2