Nuclear Medicine and Biology
Volume 36, Issue 4 , Pages 355-361, May 2009

In vivo examination of 188Re(I)-tricarbonyl-labeled trastuzumab to target HER2-overexpressing breast cancer

  • Kuo-Ting Chen

      Affiliations

    • Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan
    • ,
  • Te-Wei Lee

      Affiliations

    • Institute of Nuclear Energy Research, Longtan 32546, Taiwan
    • ,
  • Jem-Mau Lo

      Affiliations

    • Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan
    • Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 30013, Taiwan
    • Corresponding Author InformationCorresponding author. Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan. Tel.: +886 3 5727308; fax: +886 3 5718649.

Received 7 November 2008; received in revised form 5 January 2009; accepted 12 January 2009. published online 31 March 2009.

Abstract 

Introduction

Trastuzumab (Herceptin), a humanized IgG1 monoclonal antibody directed against the extracellular domain of the HER2 protein, acts as an immunotherapeutic agent for HER2-overexpressing human breast cancers. Radiolabeled trastuzumab with β- or α emitters can be used as radioimmunotherapeutic agent for the similar purpose but with additional radiation effect.

Methods

In this study, trastuzumab was labeled with 188Re for radioimmunotherapy of HER2/neu-positive breast cancer. 188Re(I)-tricarbonyl ion, [188Re(OH2)3(CO)3]+, was employed as a precursor for directly labeling the monoclonal antibody with 188Re. The immunoreactivity of 188Re(I)-trastuzumab was estimated by competition receptor-binding assay using HER2/neu-overexpressive BT-474 human breast cancer cells. The localization properties of 188Re(I)-trastuzumab within both tumor and normal tissues of athymic mice bearing BT-474 human breast cancer xenografts (HER2/neu-overexpressive) and similar mice bearing MCF-7 human breast cancer xenografts (HER2/neu-low expressive) were investigated.

Results

When incubated with human serum albumin and histidine at 25°C, 188Re(I)-trastuzumab was found to be stable within 24 h. The IC50 of 188Re(I)-trastuzumab was found to be 22.63±4.57 nM. 188Re(I)-trastuzumab was shown to accumulate specifically in BT-474 tumor tissue in in vivo biodistribution studies. By microSPECT/CT, the image of 188Re localized BT-474 tumor was clearly visualized within 24 h. In contrast, 188Re(I)-trastuzumab uptake in HER2-low-expressing MCF-7 tumor was minimal, and the 188Re image at the localization of the tumor was dim.

Conclusion

These results reveal that 188Re(I)-trastuzumab could be an appropriate radioimmunotherapeutic agent for the treatment of HER2/neu-overexpressing cancers.

Keywords: Trastuzumab, 188Re, radioimmunotherapy, 188Re(I)-tricarbonyl ion

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PII: S0969-8051(09)00009-2

doi:10.1016/j.nucmedbio.2009.01.006

Nuclear Medicine and Biology
Volume 36, Issue 4 , Pages 355-361, May 2009

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