68Ga-DOTATATE PET/CT in Gastroenteropancreatic Neuroendocrine Tumors (NETs): Pearls and Pitfalls

Introduction: Neuroendocrine tumours (NET) are a heterogeneous group of neoplasms that arise from cells of the endocrine and nervous systems. These tumours can originate from various areas of the body but are most commonly of gastroenteric or pancreatic origin (GEP NETs)[1]. NETs can be functioning, with hormone secretion and often produce symptoms, or can be non-functioning. Given the ambiguous clinical manifestations of NET, accurate assessment of the primary tumour and the extent of the metastatic spread can be challenging. The diagnostic work-up often begins with physical examination, laboratory testing for biochemical markers, and morphological imaging such as CT, MRI or US. Since most NETs are characterized by the overexpression of somatostatin receptors (SSTRs) on the cell surface, functional imaging with radiolabeled somatostatin analogues, including gallium-68 (⁶⁸Ga) labeled somatostatin analogues (⁶⁸Ga-DOTA-TOC, ⁶⁸Ga-DOTA-TATE, and ⁶⁸Ga-DOTA-NOC) for PET/CT. Expression of SSTRs is not only used for imaging but also has theranostic potential in select patients, whereby the high-level expression of somatostatin receptors is exploited to deliver targeted radiotherapy to tumor sites (peptide receptor radionuclide therapy = PRRT). The purpose of this educational exhibit is to review the pathophysiology of molecular imaging of GET NETs, and review utility of PET in the diagnosis, initial staging and restaging of patients with GEP NETs.

Methods: In this presentation we will review:

• Technical aspects of ⁶⁸Ga-DOTATATE PET/CT including patient preparation.

• Normal distribution of the tracer and potential pitfalls with this imaging modality, including uptake in normal structure and benign processes.

• Pathophysiology of molecular imaging of GEP NETs.

• The Krenning scoring scale for expression of somatostatin receptors

• Utility of 68Ga-DOTATATE PET/CT for the detection of NET, including site of primary tumor in patients with metastases from an unknown primary, and for the staging and restaging of patients with GEP NETs (including case examples).

• The available literature on the performance of ⁶⁸Ga-DOTATATE compared to conventional workup and its impact to patient management, including selection of patients for liver directed therapies and PRRT (with illustrative examples, including utility of dual tracer 68Ga-DOTATATE & FDG PET for select patients).

Results: The reviewers of this educational exhibit will learn about the normal biodistribution of 68Ga-DOTATATE, common potential pitfalls, and scoring of somatostatin receptor expression. Furthermore, they will review the utility of 68Ga-DOTATATE PET/CT in the diagnosis of NET (including in patients with metastatic NET of unknown primary site), initial staging and restaging of patients with GEP NETs, with highlights from current literature and illustrative case examples. In addition, they will learn about the role of dual tracer imaging 68Ga-DOTATATE & FDG PET in selecting patients for PRRT.

Conclusions: Given its superior accuracy compared to conventional imaging, ⁶⁸Ga-DOTATATE PET/CT has become a new reference standard for the staging and restaging of GEP NETs. Accurate staging and depiction of somatostatin receptor expression enables appropriate selection of patients for therapy (for example, for liver directed management or surgical debulking). Furthermore, the level of expression of somatostatin receptors, if present, can be scored, enabling appropriate selection of patients who would benefit from hormonal therapy or targeted radiotherapy (PRRT).

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