Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pu Jian Rd., Shanghai , 200127, China.
College of Medical Imaging, Shanghai University of Medicine & Healthy Science, Shanghai, 201318, China.
Eur J Nucl Med Mol Imaging. 2021 Dec;49(1):290-300. doi: 10.1007/s00259-021-05442-9. Epub 2021 Jun 28.
This longitudinal study aims to evaluate the performance of Ga-FAPI-04 and 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 Ga-FAPI-04 and 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 Ga-FAPI-04 and 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 Ga-FAPI-04 and F-FDG uptake (%ID/cc) at different stages of the metastasis.
Ga-FPAI-04 holds an advantage over F-FDG with higher sensitivity at the early stage of tumor metastasis. However, with the progress of tumor metastasis, uptake of Ga-FAPI-04 decreases and becomes less sensitive than F-FDG. There is also no direct correlation between uptake or S/B ratios of Ga-FAPI-04 and F-FDG during this dynamic process.
Ga-FAPI-04 is more sensitive than F-FDG in detecting the early stage of tumor metastasis, but becomes less sensitive than F-FDG at the late stage of tumor metastasis. We envision this result would be meaningful for the explanation of the Ga-FAPI-04 and F-FDG imaging both in the future clinic and preclinic studies.
本纵向研究旨在评估 Ga-FAPI-04 和 F-FDG 的性能，并在临床前 4T1 乳腺癌模型中描绘肿瘤转移的动态过程。尽管这两种放射性配体在临床上都被广泛应用，但目前尚无研究报道它们在肿瘤转移的纵向监测中的性能。此外，之前也没有阐明成纤维细胞激活蛋白（FAP）的表达水平与肿瘤转移发展之间的相关性。在本研究中，我们评估了 Ga-FAPI-04 和 F-FDG PET 在肿瘤转移整个过程中的性能及其对肿瘤转移早期诊断的潜力。我们还阐明了在肿瘤转移的不同阶段，这两种探针摄取之间以及信号与背景（S/B）比值之间的相关性。
使用雌性 BALB/c 小鼠建立了 40 例转移性 4T1 乳腺癌小鼠模型，随后每周进行一次 Ga-FAPI-04 和 F-FDG 的纵向成像，最长可达 6 周。进行体外苏木精和伊红（H&E）和免疫组织化学（IHE）染色，以评估转移病灶上的 FAP 表达。进一步进行统计分析，以评估不同转移阶段的 Ga-FAPI-04 和 F-FDG 摄取（%ID/cc）之间的相关性。
Ga-FPAI-04 在肿瘤转移的早期阶段比 F-FDG 具有更高的灵敏度。然而，随着肿瘤转移的进展，Ga-FAPI-04 的摄取减少，其灵敏度低于 F-FDG。在这个动态过程中，Ga-FAPI-04 和 F-FDG 的摄取或 S/B 比值之间也没有直接的相关性。
Ga-FAPI-04 在检测肿瘤转移的早期阶段比 F-FDG 更敏感，但在肿瘤转移的晚期阶段，其灵敏度低于 F-FDG。我们设想，这一结果对于未来临床和临床前研究中 Ga-FAPI-04 和 F-FDG 成像的解释具有重要意义。
