We aimed to evaluate ⁶⁸Ga-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. ⁶⁸Ga-DOTATATE receptor expression was assessed using 2 measures of standardized uptake value (SUV): maximum SUV (SUV_max) and tumor-to-spleen SUV ratio (SUV_T/S). Percentage change in SUV scores after PRRT relative to baseline (ΔSUV) 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 SUV_T/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 SUV_max, there was no significant difference in progression-free survival (median survival not reached vs. 14 mo, P = 0.22). Multivariate regression analysis identified SUV_T/S as the only independent predictor for tumor progression during follow-up. In the 17 of 33 patients with clinical symptoms before PRRT, ΔSUV_T/S correlated with clinical improvement (r = 0.52, P < 0.05), whereas ΔSUV_max did not (r = 0.42, P = 0.10). Changes in the tumor markers (chromogranin A and neuron-specific enolase) did not predict ΔSUV scores, clinical improvement, or time to progression. Conclusion: Decreased ⁶⁸Ga-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; ΔSUV_T/S was superior to ΔSUV_max for prediction of outcome.

Meningiomas are known to express somatostatin receptor 2 (SSTR2). PET using the SSTR2 analog (68)Ga-DOTATATE has recently been introduced for imaging of meningiomas. However, a systematic correlation between (68)Ga-DOTATATE uptake, SSTR2 expression, and histology (including tumor-free scar tissue) is still lacking. For elucidation, we conducted this prospective study. Twenty-one adult patients with primary (n = 12) or recurrent (n = 9) meningiomas were prospectively enrolled. Preoperative MR imaging and (68)Ga-DOTATATE PET scans were fused and used for a spatially precise neuronavigated tissue-sampling procedure during tumor resection. Histopathologic diagnosis included immunohistochemical determination of SSTR2 expression. At each individual sampling site, the maximum standardized uptake value (SUVmax) of (68)Ga-DOTATATE was correlated with MR imaging findings, histology, and semiquantitative SSTR2 expression. One hundred fifteen samples (81 tumor, 34 tumor-free) were obtained. There was a significant positive correlation between SUVmax and SSTR2 expression. Receiver-operating characteristic analysis revealed a threshold of 2.3 for SUVmax to discriminate between tumor and nontumoral tissue. Regarding the detection of tumor tissue, PET imaging showed a higher sensitivity (90% vs. 79%; P = 0.049), with specificity and positive predictive values similar to MR imaging, for both de novo and recurrent tumors. (68)Ga-DOTATATE uptake correlates with SSTR2 expression and offers high diagnostic accuracy to delineate meningioma from tumor-free tissue even in recurrent tumors after previous therapy. Our findings substantiate an important role for (68)Ga-DOTATATE PET in meningioma management.

In patients with suspected but yet not localized neuroendocrine tumors (NETs), early diagnosis or reliable exclusion is crucial for optimal individual prognosis and therapy. Despite recourse to several imaging modalities, the definite diagnosis of NET can be challenging. Therefore, we tested ⁶⁸Ga-DOTATATE PET/CT as a tool for improved diagnosis in a cohort of patients with suspected, nonlocalized NET. Methods: ⁶⁸Ga-DOTATATE PET/CT recordings were obtained in 104 consecutive patients meeting at least one of the following criteria: clinical suspicion of NET (n = 70), elevated blood levels of tumor markers (n = 49), and image-based suspicion of NET (n = 53). The presence of NET was validated by histopathology (n = 49) or clinical follow-up of 107 ± 59 wk (n = 55). Results: In 36 of 104 patients (35%), NET was histologically verified, most frequently located in the small bowel (10/36), pancreas (8/36), lung (5/36), and stomach (2/36). Twelve patients had tumors of nonneuroendocrine origin, and 7 patients had benign tumors. ⁶⁸Ga-DOTATATE PET/CT identified NET in 29 of the 36 cases and excluded the presence of a NET in 61 of the 68 non-NET patients, indicating a sensitivity of 81% and specificity of 90%. The PET/CT gave a false-positive result in 7 patients and a false-negative in another 7 patients, indicating positive and negative predictive values of 81% and 90%, respectively, and an accuracy of 87%. Chromogranin A levels were significantly higher in both PET-positive patients (1,841 vs. 342 ng/mL; P < 0.05) and patients with verified NET (2,214 vs. 524 ng/mL; P < 0.05). Conclusion: In patients with suspected NETs due to clinical symptoms, elevated levels of tumor markers, or indeterminate tumors suggestive of NET, ⁶⁸Ga-DOTATATE PET/CT is highly accurate, thus supporting its use in clinical routine diagnostics.