Predicting the aggressive behavior of a heterogeneous group of pancreatic neuroendocrine neoplasms (panNENs) remains a clinical challenge. Some panNENs are indolent, and some behave aggressively and metastasize to regional lymph nodes or distant organs. Prediction of the aggressiveness of panNEN is the main goal of diagnostic workup and an essential basis for treatment planning.

This thesis was designed to assess prognostic factors of panNENs. The main aim was to investigate, in a prospective setting, whether the malignant potential of nonfunctional (NF) panNENs could be predicted using dual-tracer functional imaging with [68Ga]-DOTANOC and [18F]-FDG positron emission tomography/computed tomography (PET/CT). Further, the second aim of this study was to correlate immunohistochemical tissue levels of all five somatostatin receptors with the receptor density generated from [68Ga]-DOTANOC uptake in a prospective series of NF-panNENs. The third aim of this study was to evaluate prognostic clinical factors predicting recurrence and survival in a large, immunohistochemically confirmed, national cohort of panNENs (FinPanNET study).

[18F]-FDG uptake in the tumor correlated positively with the Ki-67 proliferation index (PI) and serves as a poor prognostic marker in patients with NF-panNEN. [18F]-FDG-avidity in NF-panNEN indicates a preference for surgical management. Further, SSTR5 expression in tumor samples correlated positively with Ki-67 PI and is associated with better prognosis. When all five SSTRs were analysed, SSTR2 had the highest impact on [68Ga]-DOTANOC PET signaling of panNENs.

In the 373 immunohistochemically confirmed panNEN patients, a tumor size ≥2.4 cm predicted poorer prognosis. After re-evaluation, the Ki-67 PI changed in one-third of cases, demonstrating the importance of immunohistochemical analysis for establinshing high-quality study cohorts of panNENs.