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. 2024 Dec;52(1):280-290.
doi: 10.1007/s00259-024-06873-w. Epub 2024 Aug 12.

Exploring the value of FAP-targeted PET/CT in differentiating breast cancer molecular subtypes: a preliminary study

Tianxin Liu #  1   2 , Shengnan Xu #  2 , Kai Cheng  2   3 , Jinli Pei  2 , Shijie Wang  2 , Chao Li  4 , Wanhu Li  3 , Zhiyong Yu  5 , Jinming Yu  6   7 , Jie Liu  8   9
Affiliations

Exploring the value of FAP-targeted PET/CT in differentiating breast cancer molecular subtypes: a preliminary study

Tianxin Liu et al. Eur J Nucl Med Mol Imaging. 2024 Dec.

Abstract

Purpose: This prospective study aims to evaluate the value of [18F]AlF-NOTA-fibroblast activation protein inhibitor (FAPI)-04 positron emission tomography-computed tomography (PET/CT) in predicting molecular subtypes of breast cancer.

Methods: The study consecutively recruited patients suspected of having breast cancer from a single center who were prospectively enrolled from July 2023 to May 2024 and underwent [18F]AlF-NOTA-FAPI-04 PET/CT. This study compared the differences in tracer uptake among breast cancers with different adverse prognostic factors and molecular subtypes. The classification performance for each molecular subtype of breast cancer was assessed using a receiver operating characteristic (ROC) curve.

Results: Fifty-three participants (mean age, 51 ± 11 years; 52 females) were evaluated. Breast cancer lesions with adverse prognostic factors showed higher tracer uptake. The five different molecular subtypes exhibited varying levels of uptake. The luminal A and luminal B (HER2-negative) subtypes had relatively low uptake, while the luminal B (HER2-positive), HER2-positive, and triple-negative subtypes had relatively high uptake. ROC analysis identified the max standardized uptake value (SUVmax) as a significant classifier (AUC = 0.912, P = 0.0005) for the luminal A subtype, with 100% sensitivity and 83% specificity. For predicting the luminal B (HER2-negative) subtype, SUVmax had an AUC of 0.770 (P = 0.0015). SUVmax, with an AUC of 0.781 (P = 0.003), was used to identify the triple-negative subtype tumors, resulting in a sensitivity of 100% and specificity of 51%. Lastly, the ROC curve showed the cut-off 15.40 (AUC = 0.921, P < 0.0001) could classify luminal A & luminal B (HER2-negative), and luminal B (HER2-positive) & HER2-positive & triple-negative, yielding a sensitivity of 94% and specificity of 79%.

Conclusion: The uptake of [18F]AlF-NOTA-FAPI-04 is significantly correlated with the molecular subtypes of breast cancer, and [18F]AlF-NOTA-FAPI-04 PET/CT is a potential tool for noninvasive identification of luminal A subtypes and guidance of FAP-targeted therapies.

Keywords: Breast cancer; Fibroblast activation protein; Molecular subtype; PET/CT.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study complied with the Declaration of Helsinki. It was approved by the Institutional Ethics Committee of the Affiliated Cancer Hospital of Shandong First Medical University (institutional review board approval no. SDZLEC2021–112–02), and written informed consent was obtained from all the participants. Consent for publication: The participants consented to publish anonymized data and associated images or materials. Competing interests: All authors declare no potential conflicts of interest.

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