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68Ga-TP1580 as a novel molecular probe for HER2-positive tumor imaging using MicroPET

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Abstract

HER2 is an attractive target for the treatment of breast cancer. 99Tcm-labeled HER2-specific binding to the small molecule mimetic peptide B2-S22-AFA shows the potential of detecting HER2 expression in vivo (Zhang in Transl Oncol 10:518–526, 2017). However, the low resolution of SPECT-CT imaging and the inability to quantitatively analyze may partially limit its wide use.68Ga is an excellent PET radionuclide due to availability, nearly quantitative reaction, and short physical half-life. In this study, 68Ga-labeled-NOTA- B2-S22-AFA (hereinafter referred to as 68Ga-TP1580) was applied for PET-CT imaging in HER2 breast cancer xenografts mice. In vitro studies and MicroPET imaging were performed in the SKBR-3 breast cancer model. 68Ga-TP1580 could be produced within 20 min with 93.2 ± 2.1% yield and the radiochemical purity was greater than 95%. The tracer was stable in PBS and human serum for at least 2 h. MicroPET imaging revealed that the SKBR-3 xenografts were visualized and the tumor uptakes were 1.22 ± 0.04, 0.71 ± 0.07, and 0.43 ± 0.04% ID/g at 0.5 h, 1 h, and 2 h.The corresponding tumor-to-blood and tumor-to-muscle ratios were 1.05 ± 0.06, 1.34 ± 0.21, and 1.33 ± 0.57, respectively, and 4.02 ± 1.39, 7.47 ± 2.86, and 5.82 ± 1.98 at 0.5 h, 1 h, and 2 h. No significant decrease in tumor uptake of 68Ga-TP1580 was seen after injection of excess unlabeled TP1580.In conclusion, TP1580 can be labeled by 68Ga with high radiochemical purity (> 95%), good vitro stability (keep consistent radiochemical purity > 95% for more than 2 h).68Ga-TP1580 can combine with target tissue and show some tumor uptake in SKBR-3 xenografts, but not be blocked by NOTA-B2-S22-AFA which indicates poor specificity.

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Acknowledgements

This work was partially supported by National Natural Science Foundation 91180344.

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Authors and Affiliations

  1. Jiangxi Cancer Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China

    Jinxiu Zhong

  2. Key Laboratory of Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 210463, Jiangsu, China

    Donghui Pan

  3. Department of Nuclear Medicine/Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Yan-xing Guan

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Zhong, J., Pan, D. & Guan, Yx. 68Ga-TP1580 as a novel molecular probe for HER2-positive tumor imaging using MicroPET. J Radioanal Nucl Chem 331, 1531–1543 (2022). https://doi.org/10.1007/s10967-022-08236-x

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