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Diagnostic efficacy of [68Ga]Ga-DOTA-GPFAPI-04 in patients with solid tumors in a head-to-head comparison with [18F]F-FDG: results from a prospective clinical study

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

Abstract

Purpose

To identify the biodistribution and diagnostic performance of a novel fibroblast activation protein (FAP) targeted positron emission tomography (PET) tracer, [68Ga]Ga-DOTA-GPFAPI-04, in patients with solid tumors in a head-to-head comparison with [18F]F-FDG.

Methods

Twenty-six patients histologically proven with cancers of nasopharyngeal (n = 5), esophagus (n = 5), gastro-esophagus (n = 1), stomach (n = 7), liver (n = 3), and colorectum (n = 5) were recruited for [68Ga]Ga-DOTA-GPFAPI-04 and [18F]F-FDG PET/CT scans on consecutive days. The primary endpoint was the diagnostic efficacy, with the histological diagnosis and the follow-up results selected as the gold standard. The secondary endpoint was the background uptake pattern. Two experienced nuclear medicine physicians who were blinded to the gold standard results while having essential awareness of the clinical context reviewed the images and labeled lesions by consensus for subsequent software-assisted lesion segmentation. Additionally, background organs were automatically segmented, assisted by artificial intelligence. Volume, mean, and maximum standard uptake values (SUVmean and SUVmax) of all segmentations were recorded. P < 0.05 was deemed as statistically significant.

Results

Significant glandular uptake of [68Ga]Ga-DOTA-GPFAPI-04 was detected in the thyroid, pancreas, and submandibular glands, while moderate uptake was observed in the parotid glands. The myocardium and myometrium exhibited 2–3 times higher uptake of the radiotracer than that of the background levels in blood and liver. A total of 349 targeted lesions, consisting of 324 malignancies and 25 benign lesions, were segmented. [68Ga]Ga-DOTA-GPFAPI-04 is more sensitive than [18F]F-FDG, especially for abdominopelvic dissemination (1.000 vs. 0.475, P < 0.001). Interestingly, [18F]F-FDG demonstrated higher sensitivity for lung metastasis compared to [68Ga]Ga-DOTA-GPFAPI-04 (0.845 vs. 0.682, P = 0.003). The high glandular uptake made it difficult to delineate lesions in close proximity and masked two metastatic lesions in these organs.

Conclusion

Despite prominent glandular uptake, [68Ga]Ga-DOTA-GPFAPI-04 demonstrates favorable diagnostic performance. It is a promising probe scaffold for further development of FAP-targeted tumor theranostic agents.

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Data availability

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

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Funding

This work was supported by the fund from the National Natural Science Foundation of China (81971645 and U2267221), Guangdong Provincial People’s Hospital (KY0120211130), Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (2022B1212010011), Shanghai Municipal Science and Technology Major Project (TM202301H003), Gansu Science and Technology Major Project (23ZDFA014), and Shandong Laboratory Program (SYS202205).

Author information

Author notes

  1. Hui Yuan, Entao Liu and Guojin Zhang contributed equally to this work.

Authors and Affiliations

  1. PET Center, Department of Nuclear Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan Er Road, Guangzhou, China

    Hui Yuan, Entao Liu, Guojin Zhang, Qing Zhang, Yuxiang Shang & Lei Jiang

  2. Institute of Molecular Medicine, College of Life and Health Sciences, Northeastern University, Shenyang, China

    Chaoquan Lai

  3. State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

    Zhen Cheng

  4. Drug Discovery Shandong Laboratory, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong, China

    Zhen Cheng

  5. University of Chinese Academy of Sciences, Beijing, China

    Zhen Cheng

  6. Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, China

    Lei Jiang

Authors
  1. Hui Yuan
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Contributions

Lei Jiang and Zhen Cheng designed the study, Hui Yuan, Entao Liu, Qing Zhang, and Yuxiang Shang collected PET/CT data, Guojin Zhang and Chaoquan Lai synthesized the tracer, Hui Yuan and Entao Liu analyzed the data and carried out the statistical analysis, and all authors wrote and approved the final manuscript.

Corresponding authors

Correspondence to Zhen Cheng or Lei Jiang.

Ethics declarations

Ethical approval

This is a prospective study (NCT06186427), locally approved by the Ethics Committee of Guangdong Provincial People’s Hospital (No. XJS2023-005-01) and conducted following the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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All subjects gave written consent before participating in the study.

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The authors affirm that all human participants involved in this study have signed the consent form and agreed to the publication of their medical imaging and records in an anonymized format for the purposes of scientific research.

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Yuan, H., Liu, E., Zhang, G. et al. Diagnostic efficacy of [68Ga]Ga-DOTA-GPFAPI-04 in patients with solid tumors in a head-to-head comparison with [18F]F-FDG: results from a prospective clinical study. Eur J Nucl Med Mol Imaging (2024). https://doi.org/10.1007/s00259-024-06756-0

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