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

This longitudinal study aims to evaluate the performance of ${}^{68}$Ga-FAPI-04 and ${}^{18}$F-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 ${}^{18}$F-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. 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 ${}^{18}$F-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 ${}^{18}$F-FDG uptake (%ID/cc) at different stages of the metastasis. ${}^{68}$Ga-FPAI-04 holds an advantage over ${}^{18}$F-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 ${}^{18}$F-FDG. There is also no direct correlation between uptake or S/B ratios of ${}^{68}$Ga-FAPI-04 and ${}^{18}$F-FDG during this dynamic process. ${}^{68}$Ga-FAPI-04 is more sensitive than ${}^{18}$F-FDG in detecting the early stage of tumor metastasis, but becomes less sensitive than ${}^{18}$F-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 ${}^{18}$F-FDG imaging both in the future clinic and preclinic studies.