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  • [Pharmaceutics.] Therapeutic Response Monitoring with 89Zr-DFO-Pertuzumab in HER2-Positive and Trastuzumab-Resistant Breast Cancer Models

    [Pharmaceutics.] Therapeutic Response Monitoring with 89Zr-DFO-Pertuzumab in HER2-Positive and Trastuzumab-Resistant Breast Cancer ModelsHER2-양성 및 Trastuzumab -내성 유방암 모델에서 89Zr-DFO-Pertuzumab 치료 반응 모니터링

    KIRAMS / 강민우, 신종일, 이태섭*

  • 출처
    Pharmaceutics.
  • 등재일
    2022
  • 저널이슈번호
    14, 1338.
  • 내용

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    Abstract
    Immuno-positron emission tomography (PET) has great potential to evaluate the target expression level and therapeutic response for targeted cancer therapy. Immuno-PET imaging with pertuzumab, due to specific recognition in different binding sites of HER2, could be useful for the determination of the therapeutic efficacy of HER2-targeted therapy, trastuzumab, and heat shock protein 90 (HSP90) inhibitor, in HER2-expressing breast cancer. The aim of this study is to evaluate the feasibility of monitoring therapeutic response with 89Zr-DFO-pertuzumab for the treatment of HER2-targeted therapeutics, trastuzumab, or the HSP90 inhibitor 17-DMAG, in trastuzumab-resistant JIMT-1 breast cancer models. We prepared an immuno-PET imaging agent using desferoxamine (DFO)-pertuzumab labeled with 89Zr and performed the biodistribution and PET imaging in breast cancer xenograft models for monitoring therapeutic response to HER2-targeted therapy. 89Zr-DFO-pertuzumab was successfully prepared and showed specific binding to HER2 in vitro and clearly visualized HER2 expressing JIMT-1 tumors. 89Zr-DFO-pertuzumab had prominent tumor uptake in HER2 expressing JIMT-1 tumors. JIMT-1 tumors showed trastuzumab-resistant and HSP90 inhibitor sensitive characterization. In immuno-PET imaging, isotype antibody-treated JIMT-1 tumors had similar uptake in trastuzumab-treated JIMT-1 tumors, but 17-DMAG-treated JIMT-1 tumors showed greatly reduced uptake compared to vehicle-treated tumors. Additionally, HER2 downregulation evaluated by immuno-PET imaging was verified by western blot analysis and immunofluorescence staining which resulted in a significant reduction in the tumor’s HER2 level in 17-DMAG-treated JIMT-1 tumors. 89Zr-DFO-pertuzumab immuno-PET may be clinically translated to select pertinent patients for HER2-targeted therapy and to monitor the therapeutic response in HER2-positive cancer patients under various HER2-targeted therapeutics treatments.

     

    유방암의 HER2 표적 치료제인 허셉틴에 내성을 나타내고 HSP90 억제제에 민감성을 나타내는 유방암 모델에서 89Zr 표지 Pertuzumab 항체(면역 PET 영상제)를 이용하여 치료효과 평가에 활용할 수 있음을 제시함.

     

     

     Affiliations

     Minwoo Kang1,† , Jong Il Shin1,†, Sangjin Han1, Jung Young Kim1, Jeonghoon Park2, Kwang Il Kim1, Joo Hyun Kang1 and Tae Sup Lee1,*
     
    1 Division of RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), 75 Nowon-ro, Nowon-gu, Seoul 01812, Korea
    2 Korea Atomic Energy Research Institute (KAERI), 29 Geumgu-gil, Jeongeup-si 56212, Korea
    * Author to whom correspondence should be addressed.
    † These authors contributed equally to this work.

     

  • 키워드
    breast cancer; HER2; trastuzumab; pertuzumab; heat shock protein 90 (HSP90); 17-DMAG; Zirconium-89; positron emission tomography (PET)
  • 연구소개
    유방암의 HER2 발현의 표적 치료제의 효과적인 평가를 위한 면역 PET (Immuno-PET) 영상제 개발 및 표적 치료제인 허셉틴과 HSP90 억제제를 이용하여 면역 PET 영상제의 유효성을 평가한 연구입니다.
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