Targeted gadofullerene for sensitive magnetic resonance imaging and risk-stratification of breast cancer

Nat Commun. 2017 Sep 25;8(1):692. doi: 10.1038/s41467-017-00741-y.

Abstract

Molecular imaging of cancer biomarkers is critical for non-invasive accurate cancer detection and risk-stratification in precision healthcare. A peptide-targeted tri-gadolinium nitride metallofullerene, ZD2-Gd3N@C80, is synthesised for sensitive molecular magnetic resonance imaging of extradomain-B fibronectin in aggressive tumours. ZD2-Gd3N@C80 has superior r 1 and r 2 relaxivities of 223.8 and 344.7 mM-1 s-1 (1.5 T), respectively. It generates prominent contrast enhancement in aggressive MDA-MB-231 triple negative breast cancer in mice at a low dose (1.7 µmol kg-1, 1 T), but not in oestrogen receptor-positive MCF-7 tumours. Strong tumour contrast enhancement is consistently observed in other triple negative breast cancer models, but not in low-risk slow-growing tumours. The dose of the contrast agent for effective molecular MRI is only slightly lower than that of ZD2-Cy5.5 (0.5 µmol kg-1) in fluorescence imaging. These results demonstrate that high-sensitivity molecular magnetic resonance imaging with ZD2-Gd3N@C80 may provide accurate detection and risk-stratification of high-risk tumours for precision healthcare of breast cancer.Molecular MRI is a powerful clinical tool for non-invasive detection of cancer biomarkers. Here, the authors develop a targeted peptide gadofullerene contrast agent that can sensitively distinguish between breast cancers of different aggressiveness.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Female
  • Fullerenes / analysis*
  • Fullerenes / chemistry
  • Gadolinium / analysis
  • Gadolinium / chemistry
  • Humans
  • MCF-7 Cells
  • Magnetic Resonance Imaging
  • Mice
  • Precision Medicine / methods
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Fullerenes
  • Gadolinium