68Ga-DOTATATE PET/CT for the Early Prediction of Response to Somatostatin Receptor-Mediated Radionuclide Therapy in Patients with Well-Differentiated Neuroendocrine Tumors

We aimed to evaluate Ga-68-DOTATATE PET/CT for the early prediction of time to progression and clinical outcome after a first cycle of peptide receptor radionuclide treatment (PRRT) in a cohort of patients with well-differentiated neuroendocrine tumors. Methods: Thirty-three consecutive patients (22 men and 11 women; mean age +/- SD, 57.8 +/- 12.1 y) were investigated at baseline and again 3 mo after initiation of the first cycle of PRRT. Ga-68-DOTATATE receptor expression was assessed using 2 measures of standardized uptake value (SUV): maximum SUV (SUVmax) and tumor-to-spleen SUV ratio (SUVT/S). Percentage change in SUV scores after PRRT relative to baseline (Delta SUV) was calculated. After completing 1-3 cycles of PRRT, patients entered the follow-up study, for estimation of time to progression. According to the Response Evaluation Criteria in Solid Tumors, progression was defined on the basis of contrast-enhanced CT. Clinical symptoms, as well as the tumor markers chromogranin A and neuron-specific enolase, were also recorded during regular follow-up visits. Results: The 23 of 31 patients with decreased SUVT/S after the first PRRT cycle had longer progression-free survival than did the 8 of 31 patients with stable or increased scores (median survival not reached vs. 6 mo, P = 0.002). For the 18 of 33 patients showing a reduction in SUVmax, there was no significant difference in progression-free survival (median survival not reached vs. 14 mo, P = 0.22). Multivariate regression analysis identified SUVT/S as the only independent predictor for tumor progression during follow-up. In the 17 of 33 patients with clinical symptoms before PRRT, Delta SUVT/S correlated with clinical improvement (r = 0.52, P < 0.05), whereas Delta SUVmax did not (r = 0.42, P = 0.10). Changes in the tumor markers (chromogranin A and neuron-specific enolase) did not predict Delta SUV scores, clinical improvement, or time to progression. Conclusion: Decreased Ga-68-DOTATATE uptake in tumors after the first cycle of PRRT predicted time to progression and correlated with an improvement in clinical symptoms among patients with well-differentiated neuroendocrine tumors; Delta SUVT/S was superior to Delta SUVmax for prediction of outcome.