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[18F] AlF-NOTA-FAPI-04 PET/CT can predict treatment response and survival in patients receiving chemotherapy for inoperable pancreatic ductal adenocarcinoma

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Abstract

Purpose

We investigated whether uptake of [18F] AlF-NOTA-FAPI-04 on positron emission tomography/computed tomography (PET/CT) could predict treatment response and survival in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

We prospectively evaluated 47 patients with histopathologically confirmed primary PDAC who provided pretreatment [18F] AlF-NOTA-FAPI-04 scans to detect fibroblast activation protein (FAP) on the tumor surface by uptake of [18F] AlF-NOTA-FAPI-04. PDAC specimens were immunohistochemically stained with cancer-associated fibroblast (CAF) markers. We obtained a second PET scan after one cycle of chemotherapy to study changes in FAPI uptake variables from before to during treatment. Correlations between baseline PET variables and CAF-related immunohistochemical markers were assessed with Spearman’s rank test. Cox regression and Kaplan–Meier methods were used to assess relationships between disease progression and potential predictors. Receiver operating characteristic (ROC) curve analysis was used to define the optimal cut-off points for distinguishing patients according to good response vs. poor response per RECIST v.1.1.

Results

The FAPI PET variables maximum and mean standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion FAP expression (TLF) were positively correlated with CAF markers (FAP, α-smooth muscle actin, vimentin, S100A4, and platelet-derived growth factor receptor α/β, all P < 0.05). MTV was associated with survival in patients with inoperable PDAC (all P < 0.05). Cox multivariate regression showed that MTV was associated with overall survival (MTV hazard ratio [HR] = 1.016, P = 0.016). Greater changes from before to during chemotherapy in SUVmax, MTV, and TLF were associated with good treatment response (all P < 0.05). ΔMTV, ΔTLF, and ΔSUVmax had larger areas under the curve than ΔCA19-9 for predicting treatment response. Kaplan–Meier analysis showed that the extent of change in MTV and TLF from before to after treatment predicted progression-free survival, with cut-off values (based on medians) of − 4.95 for ΔMTV (HR = 8.09, P = 0.013) and − 77.83 for ΔTLF (HR = 4.62, P = 0.012).

Conclusions

A higher baseline MTV on [18F] AlF-NOTA-FAPI-04 scans was associated with poorer survival in patients with inoperable PDAC. ΔMTV was more sensitive for predicting response than ΔCA19-9. These results are clinically meaningful for identifying patients with PDAC who are at high risk of disease progression.

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Data availability

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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Acknowledgements

We would like to thank the staff at PET/CT center, Shandong Cancer Hospital, for their contributions to tracer preparation and PET/CT imaging.

Funding

This work was supported by the following grants: National Natural Science Foundation of China (82272753), Young TaiShan Scholars and Academic Promotion Program of Shandong First Medical University (2019RC003), Shandong Provincial Natural Science Foundation(ZR2021LZL002), Bethune Cancer Radiotherapy Translational Medicine Research Fund (flzh202103).

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  1. Ziyuan Zhu and Kai Cheng made equal contributions to this work

Authors and Affiliations

  1. School of Clinical Medicine, Weifang Medical University, Weifang, China

    Ziyuan Zhu, Fuhao Wang & Jinbo Yue

  2. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, China

    Ziyuan Zhu, Kai Cheng, Zhang Yun, Xiang Zhang, Xiaoyu Hu, Jing Liu, Zheng Fu & Jinbo Yue

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

    Kai Cheng & Zheng Fu

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Contributions

Jinbo Yue conceived and designed the study. Ziyuan Zhu participated in the experimental design and conduct and drafted the manuscript. Kai Cheng was responsible for preparation of the [18F] AlF-NOTA-FAPI-04. Ziyuan Zhu and Jing Liu were responsible for collecting PET/CT images. Zheng Fu and Yun Zhang carried out the nuclear medicine. Zheng Fu and Jinbo Yue assessed responses on the images per the RECIST system (v.1.1). Xiang Zhang did the pathology analyses. Fuhao Wang was responsible for data analysis. All authors read and approved the final manuscript.

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Correspondence to Zheng Fu or Jinbo Yue.

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Zhu, Z., Cheng, K., Yun, Z. et al. [18F] AlF-NOTA-FAPI-04 PET/CT can predict treatment response and survival in patients receiving chemotherapy for inoperable pancreatic ductal adenocarcinoma. Eur J Nucl Med Mol Imaging 50, 3425–3438 (2023). https://doi.org/10.1007/s00259-023-06271-8

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