PET Imaging of Fibroblast Activation Protein in Various Cancers Using [18F]AlF‑NOTA‑FAPI‑04: Comparison with 18F-FDG in a Single-Center, Prospective Study

Liping Yang; Liang Cheng; Yuchao Xu; Hongchao Ding; Xing Gao; Zhengsong Chang; Kezheng Wang

doi:10.1016/j.acra.2024.04.017

PET Imaging of Fibroblast Activation Protein in Various Cancers Using [¹⁸F]AlF‑NOTA‑FAPI‑04: Comparison with ¹⁸F-FDG in a Single-Center, Prospective Study

Acad Radiol. 2024 Apr 23:S1076-6332(24)00226-5. doi: 10.1016/j.acra.2024.04.017. Online ahead of print.

Authors

Liping Yang¹, Liang Cheng¹, Yuchao Xu², Hongchao Ding³, Xing Gao³, Zhengsong Chang⁴, Kezheng Wang⁵

Affiliations

¹ Department of PET-CT, Harbin Medical University Cancer Hospital, Harbin, China.
² School of Nuclear Science and Technology, University of South China, Hunan, China.
³ Department of Physical Diagnostics, Heilongjiang Provincial Hospital, Harbin, China.
⁴ Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.
⁵ Department of PET-CT, Harbin Medical University Cancer Hospital, Harbin, China. Electronic address: wangkezheng9954001@163.com.

PMID: 38658210
DOI: 10.1016/j.acra.2024.04.017

Abstract

Rationale and objectives: Targeting fibroblast-activation protein is a newer diagnostic approach for the visualization of tumor stroma, and a novel aluminum-[¹⁸F] fluoride (Al¹⁸F)-labeled fibroblast-activation protein inhibitor-4 (FAPI-04), hereafter [¹⁸F] AlF-NOTA-FAPI-04, presents a promising alternative to gallium 68 (⁶⁸Ga)-labeled FAPI owing to its relatively longer half-life. This study sought to evaluate the clinical usefulness of [¹⁸F] AlF-NOTA-FAPI-04 PET/CT for the diagnosis of various types of cancer, compared to [¹⁸F] FDG PET/CT.

Materials and methods: In this prospective study conducted from October 2021 to January 2024, a total of 148 patients with 16 different tumor entities underwent contemporaneous ¹⁸F-FDG and ¹⁸F-FAPI-04 PET/CT either for an initial assessment or for recurrence detection. Uptake of ¹⁸F-FDG and ¹⁸F-FAPI-04 was quantified by the maximum standard uptake value (SUV max). Diagnostic sensitivity, specificity, and accuracy were compared by using the McNemar test between these two imaging agents.

Results: ¹⁸F-FAPI-04 PET/CT could clearly depict 16 different types of cancer with excellent image contrast, thereby leading to a higher detection rate of primary tumors than did ¹⁸F-FDG PET/CT (98.06% vs. 81.55%, P＜0.001). In per-lymph node analysis, the sensitivity, specificity, and accuracy in the diagnosis of metastatic lymph nodes were 92.44%, 90.44%, and 91.56%, respectively, which was much higher than that ¹⁸F-FDG PET/CT (80.23%, 79.41%, and 79.87%, respectively). Meanwhile, ¹⁸F-FAPI-04 PET/CT outperformed ¹⁸F-FDG PET/CT in identifying more suspected distant metastases (86.57% vs. 74.13%, P＜0.001). Furthermore, ¹⁸F-FAPI-04 PET/CT upgraded tumor staging in 36/101 patients (35.6%), and detected tumor recurrence or metastases in 43/47 patients (91.49%).

Conclusion: Our findings demonstrated that primary and metastatic lesions in patients with various types of malignant tumors are well-visualized on ¹⁸F-FAPI-04 PET/CT, which exhibited a superior diagnostic performance than ¹⁸F-FDG PET/CT. Moreover, ¹⁸F-FAPI-04 PET/CT is a promising tool for tumor staging and follow-up of various malignancies.

Keywords: Cancer-associated fibroblasts; FAPI PET/CT; FDG PET/CT; Tumor restaging; Various cancer diseases.