Theranostics 2016; 6(11):1780-1791. doi:10.7150/thno.14280

Research Paper

Active-target T1-weighted MR Imaging of Tiny Hepatic Tumor via RGD Modified Ultra-small Fe3O4 Nanoprobes

Zhengyang Jia1,*, Lina Song1,*, Fengchao Zang2, Jiacheng Song3, Wei Zhang1, Changzhi Yan1, Jun Xie1, Zhanlong Ma3, Ming Ma1, Gaojun Teng2, Ning Gu1,✉, Yu Zhang1,✉

1. State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing 210096, China
2. Jiangsu Key Laboratory of Molecular and Functional Imaging, Medical School, Southeast University, Nanjing 210009, China
3. Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
* These authors contributed equally to this work.

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Citation:
Jia Z, Song L, Zang F, Song J, Zhang W, Yan C, Xie J, Ma Z, Ma M, Teng G, Gu N, Zhang Y. Active-target T1-weighted MR Imaging of Tiny Hepatic Tumor via RGD Modified Ultra-small Fe3O4 Nanoprobes. Theranostics 2016; 6(11):1780-1791. doi:10.7150/thno.14280. Available from http://www.thno.org/v06p1780.htm

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Abstract

Developing ultrasensitive contrast agents for the early detection of malignant tumors in liver is highly demanded. Constructing hepatic tumors specific targeting probes could provide more sensitive imaging information but still faces great challenges. Here we report a novel approach for the synthesis of ultra-small Fe3O4 nanoparticles conjugated with c(RGDyK) and their applications as active-target T1-weighted magnetic resonance imaging (MRI) contrast agent (T1-Fe3O4) for imaging tiny hepatic tumors in vivo. RGD-modified T1-Fe3O4 nanoprobes exhibited high r1 of 7.74 mM-1s-1 and ultralow r2/r1 of 2.8 at 3 T, reflecting their excellent T1 contrast effect at clinically relevant magnetic field. High targeting specificity together with favorable biocompatibility and strong ability to resist against non-specific uptake were evaluated through in vitro studies. Owing to the outstanding properties of tumor angiogenesis targeting with little phagocytosis in liver parenchyma, hepatic tumor as small as 2.2 mm was successfully detected via the T1 contrast enhancement of RGD-modified T1-Fe3O4. It is emphasized that this is the first report on active-target T1 imaging of hepatic tumors, which could not only significantly improve diagnostic sensitivity, but also provide post therapeutic assessments for patients with liver cancer.

Keywords: T1-Fe3O4 nanoprobes, RGD-modified, active-target, tiny hepatic tumor imaging, high diagnostic sensitivity