Beyond the visible: molecular imaging of aggressive epithelial solid tumors

Abstract

This thesis aims to improve surgical outcomes in pancreatic ductal adenocarcinoma (PDAC) and epithelial ovarian cancer (EOC) through tumor-targeted molecular imaging. Accurate pre- and intra-operative imaging is critical in these cancers, as conventional modalities (CT, MRI, ultrasound) have limitations, particularly after neoadjuvant therapy. Molecular imaging techniques such as near-infrared fluorescence (NIRF) and positron emission tomography (PET) provide functional and real-time tumor visualization, supporting more precise resection.

Part I identifies novel imaging targets. In PDAC, integrin αvβ6 and CEACAM5 emerged as promising targets to distinguish viable tumor from therapy-induced fibrosis after FOLFIRINOX. In EOC, EpCAM showed potential as an alternative to folate receptor-α, reducing false-positive lymph node detection. A transcriptome-based approach further identified B7-H4 as a potential new EOC imaging target, highlighting the need for protein-level validation.

Part II evaluates new tracers. Novel FAP-targeted NIRF probes demonstrated specific tumor binding and favorable tumor-to-background ratios in preclinical models. A phase I study of an FR-targeted PET tracer in advanced EOC confirmed safety but showed limited clinical utility. Part III explores dual-target imaging (GRPR and αvβ6) to address tumor heterogeneity and presents a consensus supporting NIRF imaging in pancreatic cancer surgery.