Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Comparison and evaluation of 89Zr-labeled trastuzumab and Thio-trastuzumab : a potential immuno-PET probe for HER2-positive carcinomas

  • Un Chol Shin (School of Health and Environmental Science, College of Health Science, Korea University) ;
  • Seoku Bae (School of Health and Environmental Science, College of Health Science, Korea University) ;
  • Suk-man Kim (Department of Public Health Sciences, Graduate School, Korea University) ;
  • Min-Woo Lee (Cardiovascular Research Institute, Korea University) ;
  • Han Sang Jin (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Hyun Park (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Kyo Chul Lee (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Jung Young Kim (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Ji Woong Lee (Department of Medical Laboratory Science, Seoyeong University)
  • Received : 2021.12.16
  • Accepted : 2021.12.28
  • Published : 2021.12.30
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Abstract

89Zr is a positron-emitting radioisotope, which has known as well-suited radioisotope for use in a monoclonal antibody-based imaging agent for immuno-PET. The purpose of this study was to quantitatively evaluate the diagnostic ability of general trastuzumab and thio-trastuzumab as HER2 positive receptors based on Df hexadentate iron chelator. Desferrioxamine-p-SCN (Df-Bz-NCS) and desferroixamine-maleimide (Df-Mal) were purchased from Macrocyclics (Dallas, TX, USA). The trastuzumab was purchased from Roche (Schweiz), and thio-trastuzumab was obtained from professor Hyo-Jeong Hong group (Kangwon National University). The radioisotope 89Zr was produced by domestic purification system and KIRAMS using medical cyclotron (50 MeV, Scantronix). The conjugates of Df-trastuzumab and Df-thio-trastuzumab were prepared with Df-Bz-NCS and Df-Mal under basic aqueous solution (pH 8-9) at room temperature, respectively. The conjugates purified by PD-10 column were mixed with dried 89Zr chloride. 89Zr-labeled conjugates were purified and concentrated by Amicon ultra centrifugal filter. The preparation step and time of 89Zr-labeled conjugates was shorted as 4 steps within 2 hours. 89Zr-labeled conjugates showed the highly radiochemical purity of over 98%, and were very stable until 7 days by the analysis of radio-ITLC method. Each radio-labeled conjugates were also exhibited the highly stability in both PBS buffer and mouse serum. Immuno-PET imaging of 89Zr-labeled conjugates in mice bearing gastric cancer xenograft tumors with HER2 expression showed high tumor uptake in the NCI-N87 HER2-expressing. However, 89Zr-Df-Mal-thio-trastuzumab showed a relatively lower tumor-to-background ratio than 89Zr-Df-Bz-trastuzumab, as well as whole-body distribution. In the results, 89Zr-Df-Bz-trastuzumab was evaluated to have a relatively higher HER2 diagnostic ability than 89Zr-Df-Mal-thio-trastuzumab.

Keywords

Acknowledgement

This work was supported by Nuclear Research and Development Program of the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (NRF2021M2E7A1079168) and this research was financially supported by the Ministry of Trade, Industry and Energy, Korea, under the "Regional innovation Cluster Development Program (R&D, P0015344)" supervised by the Korea Institute for Advancement of Technology (KIAT).

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