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 r1 and r2 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-Gd3N@C80 may provide accurate detection and risk-stratification of high-risk tumours for precision healthcare of breast cancer.
Highlights
Molecular imaging of cancer biomarkers is critical for non-invasive accurate cancer detection and risk-stratification in precision healthcare
We have shown that Gd(HP-DO3A) modified with linear ZD2 peptide (Thr-Val-Arg-Thr-Ser-Ala-Asp) can be used to characterise prostate cancer aggressiveness in MRI29
The structure was characterised with MALDI-TOF mass spectrometry, indicating approximately one ZD2 peptide was conjugated to each Gd3N@C80
Summary
Molecular imaging of cancer biomarkers is critical for non-invasive accurate cancer detection and risk-stratification in precision healthcare. We synthesise a high-relaxivity-targeted contrast agent by conjugating a small peptide ZD2 to hydroxylated Gd3N@C80, ZD2-Gd3N@C80, for sensitive molecular MRI of breast cancer. MRI with the targeted contrast agent at significantly reduced doses produces strong signal enhancement in aggressive TNBC tumours, not in slowgrowing low-risk breast tumours.
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