The biology of pancreatic neuroendocrine tumors can change during the disease course. This evolution of disease can manifest through increases in tumor proliferation rate, resistance to medical therapy and/or a change in tumor hormone secretion. This study aims to characterize how the biology of pancreatic neuroendocrine tumors change over time, measured by; patient symptoms, biochemistry, contrast enhanced computed tomography, FDG-PET and core needle biopsy with histopathological analysis (Ki67 index and tumor cell differentiation). Uptake on 18F-FDG-PET will be correlated directly to tumor cell proliferation rate. Fraction of patients with spatial heterogeneity in FDG uptake as well as metachronous changes in all collected data will be documented. Biomaterial from whole blood and core needle biopsies will be characterized on the molecular level, and those findings will be integrated to the above specified clinical parameters.

Inclusion Criteria:

• Age ≥18 years

• Informed consent

• WHO performance status ≤2

• Progressive disease (as defined by the local investigator) or newly diagnosed disease (defined as prior to medical or oncological intervention except for somatostatin analogue treatment).

• Pathology confirmed diagnosis of pancreatic or duodenal neuroendocrine tumour WHO G1-G3.

  o Exception: In newly diagnosed patients with high suspicion of PNET based on clinical and radiological parameters where tissue sample have not yet been obtained. These patients may be included and subsequently excluded if pathology cannot confirm NET.

• Biopsy procedure not associated with inappropriate risk as determined by the responsible physician.

Exclusion Criteria:

• Patient does not consent

• Permanent risk factors for biopsy

  • Long term treatment with anticoagulant that cannot be temporarily paused without unacceptable risk.
  • Permanent coagulation disorder

• Pregnancy or no contraceptive in fertile women.

Patients with non-resectable metastatic pancreatic neuroendocrine tumors at the Department of Endocrine Oncology, Uppsala, Sweden.