TY - JOUR
T1 - Targeted gadofullerene for sensitive magnetic resonance imaging and risk-stratification of breast cancer
AU - Han, Zheng
AU - Wu, Xiaohui
AU - Roelle, Sarah
AU - Chen, Chuheng
AU - Schiemann, William P.
AU - Lu, Zheng Rong
N1 - Funding Information:
This research was supported in part by the National Institute of Health Grants R01 EB00489 and CA194518. Z.-R.L. is M. Frank Rudy and Margaret Domiter Rudy’s Professor of Biomedical Engineering. We thank Dr. Amita M. Vaidya for the final proof reading and editing of the manuscript.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-00741-y
DO - 10.1038/s41467-017-00741-y
M3 - Article
C2 - 28947734
AN - SCOPUS:85029852205
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 692
ER -