MDSCs-targeted positron emission tomography identifies the pre-metastatic niche and informs risk-stratified intervention of postoperative metastasis

[ 18 F]FETQA‑PET visualizes MDSCs‑driven pre‑metastatic niches non‑invasively. • Preoperative lung uptake of [ 18 F]FETQA predicts postoperative metastasis. • [ 18 F]FETQA‑PET‑based risk stratification guides adjuvant therapy selection. • [ 18 F]FETQA‑PET enables monitoring of therapy response targeting pre‑metastatic niches. Postoperative metastasis persists as a predominant cause of mortality in solid tumors, largely driven by the establishment of the immunosuppressive pre-metastatic niche. The development of effective interventional strategies is currently hindered by the inability to detect the pre-metastatic niche within anatomically normal tissues. To address this limitation, we focused on myeloid-derived suppressor cells (MDSCs) as key mediators of the pre-metastatic niche and developed [ 18 F]FETQA, a novel positron emission tomography (PET) tracer targeting S100A9, a key marker of MDSCs. In spontaneous tumor metastasis models, [ 18 F]FETQA-PET allowed non-invasive visualization of the lung pre-metastatic niche, with tracer uptake demonstrating a strong positive correlation with local MDSCs burden. Preoperative quantification of [ 18 F]FETQA lung uptake serves as a significant predictor for postoperative lung metastasis development. Moreover, the integration of radiomic features with [ 18 F]FETQA lung uptake enables the construction of an enhanced predictive model (area under curve = 0.98) for stratifying postoperative metastasis risk. Finally, preoperative risk stratification utilizing [ 18 F]FETQA-PET imaging effectively identifies individuals at high-risk for metastasis and informs risk-stratified intervention, thereby alleviating the burden of the pre-metastatic niche and attenuating metastatic progression. This study establishes [ 18 F]FETQA-PET as a novel molecular imaging tool that enables non-invasive visualization of the MDSCs-driven pre-metastatic niche, functions as a predictor for postoperative lung metastasis development, and facilitates image-guided risk stratification to provide a basis for therapeutic decision making, thereby offering an integrated strategy to intercept metastatic progression. Download: Download high-res image (280KB) Download: Download full-size image