A transferrin-target magnetic/fluorescent dual-mode probe significantly enhances the diagnosis of non-small cell lung cancer
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Jiali Cai1,*, Bingxin Gu2,3,4,5,*, Fengwen Cao6, Shiyuan Liu1
1Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai, China
2Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
3Center for Biomedical Imaging, Fudan University, Shanghai, China
4Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
5Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
6School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
*These authors have contributed equally to this work
Shiyuan Liu, e-mail: firstname.lastname@example.org
Keywords: molecular imaging, transferrin, MRI/NIRF, non-small cell lung cancer, liver metastasis
Received: December 15, 2015 Accepted: April 11, 2016 Published: May 19, 2016
To enhance the diagnosis of non-small cell lung cancer (NSCLC), we prepared a dual-modal probe Cy5.5-Tf-Gd-DTPA. Gd-DTPA and near-infrared (NIR) dyes were conjugated to holo-Transferrin (Tf) sequentially, the result of ICP-AES and UV showed 25 Gd ions and 1 Cy5.5 could be loaded per protein, respectively. The calculated longitudinal relaxivity R1 of Cy5.5-Tf-DTPA-Gd was 4.21 mM-1S-1 per Gd while that of Magnevist (Gd-DTPA) was only 4.02 mM-1S-1. Confocal laser scanning microscopy and immunohistochemical analyses revealed that the Cy5.5-Tf-DTPA-Gd was localized and accumulated in cytoplasmic vesicles; the cell toxicity assay showed no apparent toxicity. MR and NIR imaging of mice with subcutaneous H1299 xenografte tumors following intravenous injection of Cy5.5-Tf-DTPA-Gd revealed a strong positive contrast of the tumors, which caused a longer lasting enhancement of the MRI signal and fluorescence signal. Taken together, these studies indicate that Cy5.5-Tf-DTPA-Gd could be a good agent for MR/NIRF dual mode applications to detect both tumor in situ and its metastasis.
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