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[18F]AlF-NOTA-FAPI-04: FAP-targeting specificity, biodistribution, and PET/CT imaging of various cancers

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

In this pilot study, we developed a new tracer, [18F]AlF-labeled FAPI-04 chelated with NOTA, denoted as [18F]AlF-NOTA-FAPI-04, and tested the specificity, biodistribution, and clinical application for PET/computed tomography (CT) imaging of various types of cancers in patients.

Methods

In vitro binding specificity of FAPI-04 to FAP was verified in U87 cells confocal of a fluorescence-labeled variant. In vivo imaging, competition, and dynamic scanning analyses were conducted to evaluate [18F]AlF-NOTA-FAPI-04 imaging in xenograft mouse model using small-animal PET/CT. The application of [18F]AlF-NOTA-FAPI-04 was analyzed by imaging different types of cancers in patients.

Results

Both in vitro and in vivo results showed high binding specificity of FAPI-04 to FAP. High intratumoral uptake and fast body clearance of the tracer were observed in the xenograft mouse model and cancer patients. High-contrast images and negligible radiation exposure to normal tissue were observed on [18F]AlF-NOTA-FAPI-04 PET/CT in 28 patients with 8 different types of cancers. Five of 28 patients underwent PET/CT scanning at 1 h, 2 h, and 4 h after intravenous injection of [18F]AlF-NOTA-FAPI-04. Seven patients with advanced lung cancer underwent dual-tracer imaging, and 44 and 37 metastatic lesions were detected by [18F]AlF-NOTA-FAPI-04 PET/CT and [18F]F-FDG PET/CT, respectively. Overall, 80.0% of metastatic lesions was identified by both [18F]AlF-NOTA-FAPI-04 and 18F-FDG, 17.8% by [18F]AlF-NOTA-FAPI-04 PET/CT only, and 2.2% by [18F]FDG PET/CT only.

Conclusion

[18F]AlF-NOTA-FAPI-04 offers high specificity as a tracer for FAP imaging and allows fast imaging with high contrast in tumors. [18F]AlF-NOTA-FAPI-04 is better at identifying metastatic lesions in patients with advanced lung cancer than [18F]FDG, and its use may facilitate tumor staging.

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Availability of data and material

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

Code availability

All software applications or custom code are available in the public repository.

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Funding

The study was supported by funds from the Major Scientific and Technological Innovation Projects of Shandong (2018YFJH0502), the Academic Promotion Program of Shandong First Medical University (2019ZL002), the foundation of National Natural Science Foundation of China (81872475, 81372413, 81627901, and 82030082), and the natural Science Foundation of Shandong Province (ZR2021QH008).

Author information

Authors and Affiliations

  1. Department of Radiology, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, China

    Yuchun Wei, Xiaoli Liu, Shuanghu Yuan & Jinming Yu

  2. Department of Radiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China

    Yuchun Wei, Xiaoli Liu, Shuanghu Yuan & Jinming Yu

  3. Department of PET/CT Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China

    Jinsong Zheng, Li Ma & Kai Cheng

  4. Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, China

    Shengnan Xu, Shijie Wang & Jinli Pei

  5. Department of PET/CT, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong, 250117, Jinan, China

    Kai Cheng

Authors
  1. Yuchun Wei
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  2. Jinsong Zheng
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  3. Li Ma
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  4. Xiaoli Liu
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  8. Kai Cheng
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  9. Shuanghu Yuan
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  10. Jinming Yu
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Contributions

Jinming Yu and Shuanghu Yuan conceived of the study and participated in its designed. Kai Cheng was responsible for the preparation of [18F]AlF-NOTA-FAPI-04 and [18F]F-FDG. Yuchun Wei participated in the experiments and drafted the manuscript. Xiaoli Liu and Shijie Wang were responsible for collecting PET/CT images. Jinsong Zheng and Li Ma carried out the nuclear medicine. Shengnan Xu and Jinli Pei carried out the pathology. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Kai Cheng, Shuanghu Yuan or Jinming Yu.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the local ethics committee of Shandong Cancer Hospital and Institute (ethical approval number: SDZLEC2021-112–02), and the patient gave written and informed consent before the study.

Consent for publication

All authors of the current manuscript meet the specified criteria for authorship and agreed to publish.

Conflict of interest

The authors declare no competing interests.

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This article is part of the Topical Collection on Translational research.

Supplementary Information

Below is the link to the electronic supplementary material.

259_2022_5758_MOESM1_ESM.pdf

Supplementary Fig. 1 Chemicalstructural formula of [18F]AlF-NOTA-FAPI-04. b: Radioactivity-high performanceliquid chromatography (HPLC) of [18F]AlF-NOTA-FAPI-04. The radiochemical purityof the final product measured by HPLC was >98% in 6.3 min, and the specificactivity was approximately 20 GBq/μmol (PDF 116 KB)

259_2022_5758_MOESM2_ESM.pdf

Supplementary Fig. 2 Comparable detection of metastases by [18F]AlF-NOTA-FAPI-04PET/CT (upper panel) and [18F]FDG PET/CT (lower panel). TheSUVmax for [18F]AlF-NOTA-FAPI-04vs [18F]FDG were compared for: (a) brain metastasis, 17.66 vs 15.09;(b) bone metastasis, 26.27 vs 17.13; (c) right adrenal metastasis, 12.12 vs5.65; and (d) liver metastasis with SUVmax=3.87 on [18F]AlF-NOTA-FAPI-04PET/CT imaging but unclear appearance on [18F]FDG PET/CT imaging (PDF 77 KB)

Supplementary Supplement 1 (DOCX 17 KB)

Supplementary Table S1 (DOCX 16 KB)

Supplementary Table S2 (DOCX 18 KB)

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Wei, Y., Zheng, J., Ma, L. et al. [18F]AlF-NOTA-FAPI-04: FAP-targeting specificity, biodistribution, and PET/CT imaging of various cancers. Eur J Nucl Med Mol Imaging 49, 2761–2773 (2022). https://doi.org/10.1007/s00259-022-05758-0

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