FAPtp2Mn-ICG

Cancer-associated fibroblasts (CAFs), characterized by the expression of fibroblast activation protein (FAP), play a pivotal role in tumor progression and therapy resistance. FAP-targeted molecular imaging offers a powerful tool for the precise visualization and quantification of CAFs within tumors. In this study, guided by molecular docking analyses, we rationally designed and synthesized two novel FAP-targeted probes, FAPtp1^Mn-ICG and FAPtp2^Mn-ICG, by conjugating FAP-targeted peptides, Mn-NOTA, and indocyanine green (ICG). These dual-modality probes, integrating magnetic resonance (MR) and near-infrared fluorescence (NIRF) imaging, were developed to enhance the evaluation of CAFs in gastric cancer. A key innovation lies in the introduction of a polyethylene glycol linker in FAPtp2^Mn-ICG, which significantly mitigates aggregation-caused quenching (ACQ) and improves NIRF imaging efficiency compared to FAPtp1^Mn-ICG. In vitro studies confirmed the high FAP-targeted specificity and biosafety of both probes. In vivo imaging in tumor-bearing mice demonstrated their excellent targeting capability and clear visualization of both subcutaneous tumors and peritoneal metastases. This work not only advances the development of FAP-targeted imaging but also provides a robust platform for the rational design of peptide-based probes for cancer diagnostics.