Patients with neuroendocrine tumors (NETs) are often treated with somatostatin analogs (SSAs) for control of symptoms and tumor growth. Such therapy could theoretically lead to misinterpretation of somatostatin receptor imaging with ⁶⁸Ga-DOTATATE PET/CT by interfering with tracer-receptor binding. Guidelines recommend an interval of 3-4 wk between the last dose and imaging. The aim of this study was to evaluate if long-acting (LA) SSA treatment changes the uptake of ⁶⁸Ga-DOTATATE in patients with NETs. Methods: From 2013 to 2016, 296 patients with, or under evaluation for, NETs were included in this prospective observational study. The effect of LA SSA on tracer uptake was evaluated in 2 main patient populations: those undergoing ⁶⁸Ga-DOTATATE PET/CT before starting LA SSA treatment and at least once afterward, and those receiving ongoing LA SSA therapy, in whom the effect of the interval between the last dose of LA SSA and the PET/CT exam was analyzed. A third, explorative, analysis was performed to evaluate if clinical disease progression, regression, or stable tumor status changed the uptake of ⁶⁸Ga-DOTATATE. In the 3 analyses, measurements of SUV_max in normal liver and tumor lesions were compared. Results: The median SUV_max in normal liver was significantly higher before treatment (8.6; interquartile range, 7.4-10.2) than after treatment initiation (6.0; 4.7-8.0) (P < 0.001). No significant changes in SUV_max were seen in tumor lesions after treatment initiation. No significant differences in SUV_max were found in normal liver or tumor lesions dependent on the interval between last dose of LA SSA and PET/CT. Conclusion: Treatment with LA SSA does not change SUV_max in tumor lesions, whereas SUV_max in normal liver is significantly lower after treatment. The findings have implications for interpretation of ⁶⁸Ga-DOTATATE PET/CT for response assessment after SSA therapy and for guidelines on discontinuation of treatment before PET/CT.

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