68Ga-FAPI-04 vs. 18F-FDG in a longitudinal preclinical PET imaging of metastatic breast cancer

Abstract

Purpose: This longitudinal study aims to evaluate the performance of ⁶⁸ Ga-FAPI-04 and ¹⁸F-FDG and to profile the dynamic process of tumor metastasis in a preclinical 4T1 breast cancer model. Although both of these two radioligands are wildly used in clinic, no study was reported on their performance in the longitudinal monitoring of tumor metastasis. Also, no correlation between the expression level of fibroblast activation protein (FAP) and the development of tumor metastasis has been elucidated previously. In this study, we evaluated the performance of ⁶⁸ Ga-FAPI-04 and ¹⁸F-FDG PET during the entire process of tumor metastasis, and their potential for the early diagnosis of tumor metastasis. We also clarified the correlation of uptakes as well as the signal-to-background (S/B) ratios between these two probes at different stages of tumor metastasis.

Methods: Forty 4T1 metastatic breast cancer murine models were established using female BALB/c mice, followed by the longitudinal imaging with ⁶⁸ Ga-FAPI-04 and ¹⁸F-FDG once a week for up to 6 weeks. In vitro hematoxylin and eosin (H&E) and immunochemistry (IHE) staining were performed to evaluate FAP expression on the metastatic lesions. Further statistical analysis was performed to evaluate the correlation of ⁶⁸ Ga-FAPI-04 and ¹⁸F-FDG uptake (%ID/cc) at different stages of the metastasis.

Results: ⁶⁸ Ga-FPAI-04 holds an advantage over ¹⁸F-FDG with higher sensitivity at the early stage of tumor metastasis. However, with the progress of tumor metastasis, uptake of ⁶⁸ Ga-FAPI-04 decreases and becomes less sensitive than ¹⁸F-FDG. There is also no direct correlation between uptake or S/B ratios of ⁶⁸ Ga-FAPI-04 and ¹⁸F-FDG during this dynamic process.

Conclusion: ⁶⁸ Ga-FAPI-04 is more sensitive than ¹⁸F-FDG in detecting the early stage of tumor metastasis, but becomes less sensitive than ¹⁸F-FDG at the late stage of tumor metastasis. We envision this result would be meaningful for the explanation of the ⁶⁸ Ga-FAPI-04 and ¹⁸F-FDG imaging both in the future clinic and preclinic studies.

Keywords: 68 Ga-FAPI-04; Fibroblast activation protein; Longitudinal PET imaging; Tumor metastasis.