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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-Gd 3 N@C80, is synthesised for sensitive molecular magnetic resonance imaging of extradomain-B fibronectin in aggressive tumours. ZD2-Gd 3 N@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 higher 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-Gd 3 N@C80 may provide accurate detection and risk-stratification of high-risk tumours for precision healthcare of breast cancer.

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