Purpose In our study, tumor heterogeneity was evaluated using the parameters skewness and kurtosis on pretreatment Ga-68 DOTA-TATE PET/CT to assess therapy responses of lesions in patients with gastroenteropancreatic neuroendocrine tumors (GEP NETs) treated with peptide receptor radionuclide therapy (PRRT). Method We retrospectively studied the texture analysis with relatively simple first-order parameters skewness and kurtosis on pretreatment Ga-68 DOTA-TATE PET/CT from 22 patients (eight females, 14 males; with a mean age: 54 +/- 11 years) with GEP NETs who were treated with 2-6 therapy cycles of Lu-177 DOTA-TATE. A total of 326 lesions of 22 patients were evaluated in terms of treatment response by Ga-68 DOTA-TATE PET/CT examination performed before and after treatment. Receiver-operating characteristic (ROC) curves were generated to assess skewness and kurtosis to discriminate between responder and nonresponder lesions. Result A total of 326 lesions of 22 patients were evaluated and 137 lesions responded partially or completely to the treatment, 189 lesions did not respond to treatment, remained stable or progressed. The skewness and kurtosis values of the lesions which did not respond to the PRRT were significantly higher than those with response to PRRT treatment (P< 0.001 andP= 0.004, respectively). However, ROC curves provided a moderate area under the curve value for skewness and a relatively low value for kurtosis (0.619 and 0.518, respectively). Conclusion Texture analysis using skewness and kurtosis of the lesions on pretreatment Ga-68 DOTA-TATE PET/CT was able to predict their responsiveness to PRRT.