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Design and preliminary assessment of 99mTc-labeled ultrasmall superparamagnetic iron oxide-conjugated bevacizumab for single photon emission computed tomography/magnetic resonance imaging of hepatocellular carcinoma

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Abstract

Hepatocellular carcinoma (HCC) has a very high incidence and mortality. Early diagnosis and timely treatments are therefore required to improve the quality of life and survival rate of HCC patients. Here, we developed a vascular endothelial growth factor (VEGF)-based multimodality imaging agent for single photon emission computed tomography (SPECT), computed tomography (CT) and magnetic resonance imaging (MRI) and used it to assess HCC mice and explore the combinative value of CT/MRI-based morphological imaging and SPECT functional imaging. HCC targeting with 125I-labeled bevacizumab monoclonal antibody (mAb) was examined using SPECT/CT in HepG2 tumor-bearing mice after intravenous mAb injection. Based on this, an integrated, bimodal, VEGF-targeted, ultrasmall superparamagnetic iron oxide (USPIO)-conjugated 99mTc-labeled bevacizumab mAb was synthesized to increase tumor penetration and accumulations. The in vivo pharmacokinetics and HepG2 tumor targeting were explored through in vivo planar imaging and SPECT/CT using a mouse model of HepG2 liver cancer. The specificity of the radiolabeled nanoparticles for HepG2 HCC was verified using in vitro immunohistochemistry and Prussian blue staining. With diethylenetriamine pentaacetic acid as a bifunctional chelating agent, USPIO-bevacizumab achieved a 99mTc labeling efficiency of >90 %. The in vivo imaging results also exhibited the targeting of USPIO on HepG2 HCC. The specificity of these results was confirmed using in vitro immunohistochemistry and Prussian blue staining. Our preliminary findings showed the potential of USPIO as an imaging agent for the SPECT/MRI of HepG2 HCC.

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Acknowledgments

This work was supported, in part, by the National Natural Science Foundation of China (NSFC) under Contract No. 81201130 and 81271608 and Young investigator start funding under contract No. Y-2013-11 from Shanghai Institute of Medical Imaging. The authors also acknowledge Drs. Yinjian Zhang and Jianpin Zhang from Fudan University Shanghai Cancer Center helping with small animal SPECT/CT imaging.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Yanzhao Zhao, Hui Tan, Bing Wu, Pengcheng Hu, Pengyue Wu, Yushen Gu, Dengfeng Cheng & Hongcheng Shi

  2. Shanghai Institute of Medical Imaging, Shanghai, 200032, China

    Yanzhao Zhao, Hui Tan, Bing Wu, Pengcheng Hu, Pengyue Wu, Yushen Gu, Dengfeng Cheng & Hongcheng Shi

  3. Med-X Research Institute of Shanghai Jiao Tong University, Shanghai, 201101, China

    Qi Yao & Chunfu Zhang

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  1. Yanzhao Zhao
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  2. Qi Yao
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  3. Hui Tan
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  4. Bing Wu
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  5. Pengcheng Hu
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  6. Pengyue Wu
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  7. Yushen Gu
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  8. Chunfu Zhang
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  9. Dengfeng Cheng
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  10. Hongcheng Shi
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Correspondence to Dengfeng Cheng or Hongcheng Shi.

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Zhao, Y., Yao, Q., Tan, H. et al. Design and preliminary assessment of 99mTc-labeled ultrasmall superparamagnetic iron oxide-conjugated bevacizumab for single photon emission computed tomography/magnetic resonance imaging of hepatocellular carcinoma. J Radioanal Nucl Chem 299, 1273–1280 (2014). https://doi.org/10.1007/s10967-013-2846-7

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  • DOI: https://doi.org/10.1007/s10967-013-2846-7

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