Liu Luoxia, Shi Yifan, He Shujie, Yang Jingfei, Song Shuang, Wang Dongdong, Wang Ziqiang, Zhou Huimin, Deng Xiaoyun, Zou Sijuan, Zhu Yuankai, Yu Bo, Zhu Xiaohua
Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
National Center for Major Public Health Events, 1095 Jiefang Ave, Wuhan, 430030, China.
Eur J Nucl Med Mol Imaging. 2025 May;52(6):2198-2211. doi: 10.1007/s00259-025-07071-y. Epub 2025 Jan 11.
Since fibroblast activation protein (FAP), one predominant biomarker of cancer associated fibroblasts (CAFs), is highly expressed in the tumor stroma of various epidermal-derived cancers, targeting FAP for tumor diagnosis and treatment has shown substantial potentials in both preclinical and clinical studies. However, in preclinical settings, tumor-bearing mice exhibit relatively low absolute FAP expression levels, leading to challenges in acquiring high-quality PET images using radiolabeled FAP ligands (FAPIs) with low molar activity, because of which a saturation effect in imaging is prone to happen. Moreover, how exactly the molar dose of FAPI administered to a mouse influences the targeted PET imaging and radiotherapy remains unclear now. Therefore, this study aims to investigate the impacts of the molar dose of the administered FAPI on FAP-targeted PET imaging and radiotherapy in mouse syngeneic tumor models.
[Ga]Ga-FAPI-04 with various molar doses of FAPI-04 was administered to wild-type 4T1 tumor-bearing mice, followed by static PET imaging. Sigmoidal curves were generated to analyze the correlation between the standard uptake value (SUV) and the administered molar doses of FAPI-04. Similarly, [Lu]Lu-DOTAGA.(SA.FAPi) with a consistent dose of radioactivity but containing different moles of DOTAGA.(SA.FAPi) were injected into 4T1 tumor-bearing mice to assess the therapeutic effect. [Ga]Ga-FAPI-04 was also applied to different tumor models for PET/CT imaging.
A gradient blocking effect was observed with increasing FAPI molar dose in [Ga]Ga-FAPI-04 PET imaging and [Lu]Lu-DOTAGA.(SA.FAPi) treatment, with various imaging and therapeutic outcomes. [Ga]Ga-FAPI-04 PET exhibit potentials to characterize murine derived FAP expression with low molar dose of administered FAPI-04 using various tumor models.
The molar dose of FAPI in [Ga]Ga/[Lu]Lu-FAPI had a substantial impact on FAP-targeted imaging and therapy in mouse syngeneic tumor models. To acquire enhanced reliability and reproducibility in preclinical situation, it is critical to carefully consider the molar dose of the radiotracer when applying radiolabeled FAP ligands to FAP-targeted imaging and radiotherapy.
成纤维细胞活化蛋白（FAP）是癌症相关成纤维细胞（CAF）的一种主要生物标志物，在各种表皮源性癌症的肿瘤基质中高度表达，在临床前和临床研究中，靶向FAP进行肿瘤诊断和治疗已显示出巨大潜力。然而，在临床前环境中，荷瘤小鼠的FAP绝对表达水平相对较低，由于使用低摩尔活度的放射性标记FAP配体（FAPIs）获取高质量PET图像存在挑战，因此成像中容易出现饱和效应。此外，给予小鼠的FAPI摩尔剂量究竟如何影响靶向PET成像和放射治疗，目前尚不清楚。因此，本研究旨在探讨给予的FAPI摩尔剂量对小鼠同基因肿瘤模型中FAP靶向PET成像和放射治疗的影响。
将不同摩尔剂量的FAPI-04的[镓]Ga-FAPI-04给予野生型荷4T1肿瘤小鼠，随后进行静态PET成像。生成S形曲线以分析标准摄取值（SUV）与给予的FAPI-04摩尔剂量之间的相关性。同样，将放射性活度一致但含有不同摩尔数的DOTAGA.(SA.FAPi)的[镥]Lu-DOTAGA.(SA.FAPi)注入荷4T1肿瘤小鼠以评估治疗效果。[镓]Ga-FAPI-04也应用于不同肿瘤模型进行PET/CT成像。
在[镓]Ga-FAPI-04 PET成像和[镥]Lu-DOTAGA.(SA.FAPi)治疗中，随着FAPI摩尔剂量增加观察到梯度阻断效应，具有各种成像和治疗结果。[镓]Ga-FAPI-04 PET有潜力使用各种肿瘤模型，以低摩尔剂量的给予的FAPI来表征小鼠来源的FAP表达。
[镓]Ga/[镥]Lu-FAPI中FAPI的摩尔剂量对小鼠同基因肿瘤模型中FAP靶向成像和治疗有重大影响。为在临床前情况下获得更高的可靠性和可重复性，在将放射性标记的FAP配体应用于FAP靶向成像和放射治疗时，仔细考虑放射性示踪剂的摩尔剂量至关重要。
