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

Abstract

Somatostatin receptor PET tracers such as [ 68 Ga-DOTA, 1-Nal 3 ]-octreotide ( 68 Ga-DOTANOC) and [ 68 Ga-DOTA,Tyr 3 ]-octreotate ( 68 Ga-DOTATATE) have shown promising results in patients with neuroendocrine tumors, with a higher lesion detection rate than is achieved with 18 F-fluorodihydroxyphenyl-Lalanine PET, somatostatin receptor SPECT, CT, or MR imaging. 68 Ga-DOTANOC has high affinity for somatostatin receptor subtypes 2, 3, and 5 (sst 2,3,5 ). It has a wider receptor binding profile than 68 Ga-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 68 Ga-DOTANOC and 68 Ga-DOTATATE PET/CT in the same patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and to evaluate the clinical impact of 68 Ga-DOTANOC PET/CT. Methods: Eighteen patients with biopsy-proven GEP-NETs were evaluated with 68 Ga-DOTANOC and 68 Ga-DOTATATE using a randomized crossover design. Labeling of DOTANOC and DOTATATE with 68 Ga 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, 18 F-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. 68 Ga-DOTANOC and 68 Ga-DOTATATE were false-negative in only 1 of 18 patients. In total, 248 lesions were confirmed by crosssectional and PET imaging. The lesion-based sensitivity of 68 Ga-DOTANOC PET was 93.5%, compared with 85.5% for 68 Ga-DOTATATE PET (P 5 0.005). The better performance of 68 Ga-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 5 0.009).This finding was less pronounced with 68 Ga-DOTANOC (P . 0.001). Altogether, 68 Ga-DOTANOC changed treatment in 3 of 18 patients (17%). Conclusion: The sst 2,3,5 -specific radiotracer 68 Ga-DOTANOC detected significantly more lesions than the sst 2 -specific radiotracer 68 Ga-DOTATATE in our patients with GEP-NETs. The clinical relevance of this finding has to be proven in larger studies.

Clinical Translation of a Click-Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

“…This is to be expected because 18 F-FET-bAG-TOCA had both renal and biliary elimination, whereas 68 Ga-based ligands have predominantly renal elimination (21)(22)(23). In our cohort of patients with liver metastases, the tumor-to-background ratio for 18 F-FET-bAG-TOCA in the liver (4.23 6 2.69) was broadly similar to that reported for 68 Ga-DOTANOC (3.4 6 2.3), 68 Ga-DOTATOC (2.8 6 1.6), and 68 Ga-DOTATATE (2.0; interquartile range, 1.4-2.7) (24)(25)(26).…”

64Cu-DOTATATE PET for Neuroendocrine Tumors: A Prospective Head-to-Head Comparison with 111In-DTPA-Octreotide in 112 Patients

“…However, because of the better sensitivity, spatial resolution, and inherently quantitative nature of PET, somatostatin receptor imaging (SRI) with PET is increasingly used. Most common is the use of the 68 Ga-labeled somatostatin analogs, for example, 68 Ga-DOTATATE (6)(7)(8)(9), 68 Ga-DOTATOC (10)(11)(12), and 68 Ga-DOTANOC (13). However, the high positron energy of 68 Ga limits spatial resolution and the short half-life of 68 min may be challenging logistically, because production has to be aligned with patients and to be repeated several times a day.…”

Approaches to Multireceptor Targeting: Hybrid Radioligands, Radioligand Cocktails, and Sequential Radioligand Applications

“…Later on, it was shown that not only sst 2 but also several other somatostatin receptor subtypes (sst 3 and sst 5 ) could be expressed concomitantly in a single NET tumor sample (4), introducing the idea that multireceptor targeting within the somatostatin receptor family may be feasible. A compound with an affinity for sst 2 , sst 3 , and sst 5 -DOTANOC-was developed and shown to label sst 2 -, sst 3 -, and sst 5 -positive tumors (5), often detecting in vivo more sites than sst 2 -selective ligands (6).…”