In vivo imaging of methionine aminopeptidase II for prostate cancer risk stratification

摘要: Prostate cancer is one of the most common malignancies worldwide, yet limited tools exist for prognostic risk stratification disease. Identification new biomarkers representing intrinsic features malignant transformation and development imaging technologies are critical improving treatment decisions patient survival. In this study, we analyzed radical prostatectomy specimens from 422 patients with localized disease to define expression pattern methionine aminopeptidase II (MetAP2), a cytosolic metalloprotease that has been identified as druggable target in cancer. MetAP2 was highly expressed 54% low-grade 59% high-grade Elevated levels at diagnosis were associated shorter time recurrence. Controlled self-assembly synthetic small molecule enabled design first MetAP2-activated positron emission tomography (PET) tracer monitoring activity vivo. The nanoparticles assembled upon activation imaged single prostate cells post-click fluorescent labeling. fluorine-18 labeled tracers successfully differentiated both knockdown inhibitor-treated human xenografts by micro-PET/CT scanning. This sensitive technology may provide tool non-invasive early therapeutic effect inhibitors anti-cancer drugs.