Development of 99mTc-conjugated JS001 antibody for in vivo mapping of PD-1 distribution in murine |
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Authors: | Xiaoyi Guo Hua Zhu Teli Liu Xiaoxia Xu Yan Kong Sheng Yao Xinan Sheng Zhi Yang |
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Affiliation: | 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China;2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing 100142, China;3. Shanghai Junshi Biosciences Co Ltd, Shanghai 201203, China |
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Abstract: | Here we reported the development of a novel immuno-SPECT tracer, namely 99mTc-JS001, to non-invasively image PD-1 expression in mice. The JS001 antibody was directly labeled by the most widely used SPECT radionuclide 99mTc with a radiochemical yield of 90%, and the specific activity was ≤74 GBq/mmol. After the radiolabeling, 99mTc-JS001 exhibited a similar immnuoaffinity to PD-1 in vitro. 99mTc-conjugated JS001 maintained intact in 5% HSA system for 24 h. S180 sarcoma xenograft-bearing Kunming mice and BGC823 gastric cancer orthotopic tumor model were built. Bio-distribution and/or immuno-SPECT studies with 99mTc-JS001 showed the antibody maintained in the blood, liver, kidneys and tumors at 1.5 ID%/g, 1.4 ID%/g, 2.0 ID%/g and 0.5 ID%/g, respectively. Also, there was a higher uptake in the BGC823 orthotopic tumor than that in the adjunct stomach. These results demonstrated that 99mTc-JS001 might have capacity to monitor the PD-1 expression in vivo, which might facilitate the anti-PD-1 antibodies treatment in preclinical models. |
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Keywords: | Corresponding authors. JS001 Technetium-99m Orthotopic gastric cancer Molecular imaging Anti-PD-1 monoclonal antibodies |
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