Abstract
This study aimed to develop and evaluate a novel fibroblast activation protein (FAP)-specific tracer, fluorine-18-labeled fibroblast activation protein inhibitor-FUSCC-07 ([18F]F-FAPI-FUSCC-07), for use in both preclinical and clinical settings. Preclinical evaluations were conducted to assess the stability and partition coefficient of [18F]F-FAPI-FUSCC-07. Experiments involving human glioma U87MG cells demonstrated its cellular uptake and inhibitory properties. Further investigations included biodistribution analysis and micropositron emission tomography/computed tomography (PET/CT) imaging in U87MG tumor-bearing mice, which revealed strong tumor uptake and prolonged retention. In the clinical setting, [18F]F-FAPI-FUSCC-07 was compared directly with [18F]F-FAPI-42 and [18F]F-FAPI-74 to evaluate its performance in imaging various cancers. By expanding the patient cohort, the study provided a more comprehensive assessment of tracer uptake in lesions. The findings demonstrated that [18F]F-FAPI-FUSCC-07 exhibited high stability in phosphate-buffered saline and fetal bovine serum, as well as hydrophilic properties. Clinical imaging results indicated significantly higher tumor uptake and improved target-to-blood pool ratios compared to the other tracers. Moreover, PET imaging of patients with diverse cancers showed that [18F]F-FAPI-FUSCC-07 consistently provided superior image contrast in most cases. These results represent the first clinical evidence supporting the feasibility of [18F]F-FAPI-FUSCC-07 for imaging across multiple tumor types. The study highlights its potential as a promising tracer for FAPI PET imaging, offering enhanced diagnostic precision and broader applicability in oncology.
Published Version
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