Normal variants, pitfalls, and interpretation challenges of somatostatin receptor PET

Somatostatin receptor (SSTR) PET has become a central imaging tool in neuroendocrine tumors (NETs), with established roles in detection, staging, restaging, and selection of patients for peptide receptor radionuclide therapy (PRRT). Despite its high sensitivity and target specificity, interpretation is not always straightforward. Physiological SSTR expression, focal variants of normal biodistribution, technical and administration-related artifacts, inflammatory conditions, and benign or malignant non-neuroendocrine lesions may all generate uptake that mimics NET involvement. Conversely, small lesion size, partial-volume effects, high physiological background, and genuinely low or absent receptor expression may reduce lesion conspicuity and lead to false-negative or underestimated disease. Interpretive challenges have also become more relevant as SSTR PET is increasingly used for quantitative, longitudinal, and theranostic assessment. Somatostatin analogue treatment can modify normal-organ biodistribution and lesion-to-background contrast, while liver and spleen uptake may vary substantially across serial examinations and should not necessarily be considered stable reference tissues. In addition, inter-lesional differences in receptor expression may have practical implications when SSTR PET is used to assess suitability for PRRT, because intense uptake in part of the disease does not necessarily imply adequate target expression across all clinically relevant lesions. This review summarizes the principal physiological variants and false-positive and false-negative findings encountered on SSTR PET and discusses contemporary pitfalls related to biodistribution, receptor heterogeneity, quantitative interpretation, and theranostic decision-making. Accurate interpretation requires integration of molecular, anatomical, and clinical information rather than reliance on isolated uptake intensity or a binary positive/negative classification.