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Comparison of renal clearance of [18F]AlF-RESCA-HER2-BCH and [18F]AlF-NOTA-HER2-BCH in mice and breast cancer patients

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Abstract

Purpose

A novel HER2 affibody-based molecular probe, [18F]AlF-RESCA-HER2-BCH, was developed for reducing renal uptake, evaluated, and compared with [18F]AlF-NOTA-HER2-BCH.

Methods

In preclinical studies, micro-PET/CT was performed using HER2-positive gastric cancer patient-derived xenografts (PDX) model at 0.5-1 (dynamic), 2, 4, and 6 h post-injection. For blocking experiment, 0.5 mg cold affibody was co-injected with probes. Biodistribution were performed on HER2-positive PDX models at 2 h post-injection. For clinical study, PET/CT images were acquired at 2 h and 4 h after injection of 231.29 ± 17.77 MBq [18F]AlF-NOTA-HER2-BCH or [18F]AlF-RESCA-HER2-BCH in five breast cancer patients (4 HER2-positive and 1 HER2-low). Standardized uptake values (SUVs) were measured in tumors and source-organs for semi-quantitative analysis. The OLINDA/EXM software (version 1.2) was used to calculate the radiation doses.

Results

[18F]AlF-NOTA-HER2-BCH and [18F]AlF-RESCA-HER2-BCH were stably labeled with [18F]F, with high binding specificity and affinity to HER2. Micro-PET/CT of both tracers could clearly visualize HER2-positive PDX tumors with high uptake of 16.24 ± 1.74% ID/g and 14.39 ± 2.45% ID/g at 2 h post-injection. The renal accumulation of [18F]AlF-RESCA-HER2-BCH was significantly lower than that of [18F]AlF-NOTA-HER2-BCH (5.16 ± 0.22% ID/g vs. 158.73 ± 5.44% ID/g at 2 h, p < 0.0001). In the clinical study, both [18F]AlF-NOTA-HER2-BCH and [18F]AlF-RESCA-HER2-BCH demonstrated favorable tumor targeting and image contrast. [18F]AlF-RESCA-HER2-BCH showed a higher SUVmax in both primary tumor and metastases, and a significantly higher target-to-nontarget ratio in metastases than [18F]AlF-NOTA-HER2-BCH. Moreover, [18F]AlF-RESCA-HER2-BCH had lower renal accumulation (43.56 ± 7.88 vs. 79.81 ± 3.81 at 2 h, p < 0.0001; 33.23 ± 6.89 vs. 78.63 ± 4.00 at 4 h, p < 0.0001) as well as a significantly lower renal absorbed dose than [18F]AlF-NOTA-HER2-BCH (0.4450 ± 0.1117 mGy/MBq vs. 0.8030 ± 0.1604 mGy/MBq, p < 0.01).

Conclusions

[18F]AlF-RESCA-HER2-BCH tended to provide better image contrast than [18F]AlF-NOTA-HER2-BCH with a higher target-to-nontarget ratio in detection of metastases. Notably, [18F]AlF-RESCA-HER2-BCH had lower renal accumulation than [18F]AlF-NOTA-HER2-BCH.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This research was supported by grants from the National Natural Science Foundation of China (NSFC) (No. 82171980 and 82171973); Capital’s Funds for Health Improvement and Research (No. 2022-2Z-2154 and 2022-2Z-2155); Beijing Hospitals Authority Deng feng Project (DFL20191102); The Pilot Project (4th Round) to Reform Public Development of Beijing Municipal Medical Research Institute (2021-1); Science Foundation of Peking University Cancer Hospital (No. 2021-4 and KC2305).

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Author notes

  1. Jiayue Liu and Xiaoyi Guo contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China

    Jiayue Liu, Xiaoyi Guo, Futao Liu, Hua Zhu, Nina Zhou & Zhi Yang

  2. Guizhou University School of Medicine, Guizhou University, Guiyang, China

    Li Wen

  3. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China

    Lixin Wang

  4. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, Beijing, China

    Guohong Song

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  1. Jiayue Liu
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Correspondence to Hua Zhu, Nina Zhou or Zhi Yang.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by Ethics Committee of Beijing Cancer Hospital and Institute (No. 2019KT114).

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Liu, J., Guo, X., Wen, L. et al. Comparison of renal clearance of [18F]AlF-RESCA-HER2-BCH and [18F]AlF-NOTA-HER2-BCH in mice and breast cancer patients. Eur J Nucl Med Mol Imaging 50, 2775–2786 (2023). https://doi.org/10.1007/s00259-023-06232-1

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