Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT Within Patients with Gastroenteropancreatic Neuroendocrine Tumors

Somatostatin receptor PET tracers such as [Ga-68-DOTA, 1-Nal(3)]-octreotide (Ga-68-DOTANOC) and [Ga-68-DOTA, Tyr(3)]-octreotate (Ga-68-DOTATATE) have shown promising results in patients with neuroendocrine tumors, with a higher lesion detection rate than is achieved with 18F-fluorodihydroxyphenyl-Lalanine PET, somatostatin receptor SPECT, CT, or MR imaging. Ga-68-DOTANOC has high affinity for somatostatin receptor subtypes 2, 3, and 5 (sst(2,3,5)). It has a wider receptor binding profile than Ga-68-DOTATATE, which is sst(2)-selective. The wider receptor binding profile might be advantageous for imaging because neuroendocrine tumors express different subtypes of somatostatin receptors. The goal of this study was to prospectively compare Ga-68-DOTANOC and Ga-68-DOTATATE PET/CT in the same patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and to evaluate the clinical impact of Ga-68-DOTANOC PET/CT. Methods: Eighteen patients with biopsy-proven GEP-NETs were evaluated with Ga-68-DOTANOC and Ga-68-DOTATATE using a randomized crossover design. Labeling of DOTANOC and DOTATATE with Ga-68 was standardized using a fully automated synthesis device. PET/CT findings were compared with 3-phase CT scans and in some patients with MR imaging, F-18-FDG PET/CT, and histology. Uptake in organs and tumor lesions was quantified and compared by calculation of maximum standardized uptake values (SUVmax) using volume computer-assisted reading. Results: Histology revealed low-grade GEP-NETs (G1) in 4 patients, intermediate grade (G2) in 7, and high grade (G3) in 7. Ga-68-DOTANOC and Ga-68-DOTATATE were false-negative in only 1 of 18 patients. In total, 248 lesions were confirmed by cross-sectional and PET imaging. The lesion-based sensitivity of Ga-68-DOTANOC PET was 93.5%, compared with 85.5% for Ga-68-DOTATATE PET (P = 0.005). The better performance of Ga-68-DOTANOC PET is attributed mainly to the significantly higher detection rate of liver metastases rather than tumor differentiation grade. Multivariate analysis revealed significantly higher SUVmax in G1 tumors than in G3 tumors (P = 0.009). This finding was less pronounced with Ga-68-DOTANOC (P > 0.001). Altogether, Ga-68-DOTANOC changed treatment in 3 of 18 patients (17%). Conclusion: The sst(2,3,5)-specific radiotracer Ga-68-DOTANOC detected significantly more lesions than the sst(2)-specific radiotracer Ga-68-DOTATATE in our patients with GEP-NETs. The clinical relevance of this finding has to be proven in larger studies.