A prospective head-to-head comparison of 68 Ga-NOTA-3P-TATE-RGD and 68 Ga-DOTATATE in patients with gastroenteropancreatic neuroendocrine tumours

Abstract

Purpose: The aim of this study was to compare ⁶⁸ Ga-NOTA-3P-TATE-RGD, a dual somatostatin receptor 2- and integrin α_Vβ₃-targeting tracer, to ⁶⁸ Ga-DOTATATE in a single group of patients with gastroenteropancreatic (GEP)-neuroendocrine tumours (NETs).

Methods: Thirty-five patients with histologically confirmed GEP-NETs (5 grade 1, 28 grade 2, and 2 grade 3 tumours) were prospectively enrolled with informed consent. The primary tumour mainly originated from the pancreas and rectum. All patients were scanned with both ⁶⁸ Ga-NOTA-3P-TATE-RGD PET/CT and ⁶⁸ Ga-DOTATATE PET/CT within a week and compared on a head-to-head basis. Sixteen patients also had conventional ¹⁸F-FDG PET/CT. Images were evaluated semi-quantitatively using maximum standardized uptake values (SUVmax) of tumour and tumour-to-background ratio.

Results: All patients had at least one positive lesion on each of the two scans. A total of 1190 and 1106 lesions were detected on ⁶⁸ Ga-NOTA-3P-TATE-RGD images and ⁶⁸ Ga-DOTATATE images, respectively (P = 0.152). ⁶⁸ Ga-NOTA-3P-TATE-RGD PET/CT revealed significantly more lesions in the liver than ⁶⁸ Ga-DOTATATE PET/CT (634 vs. 532, P = 0.021). Both tracers produced comparable results for detecting primary tumours (20 vs. 20, P = 1.000), lymph node metastases (101 vs. 102, P = 0.655), and bone metastases (381 vs. 398, P = 0.244). The tumour SUVmax in 12 patients was significantly higher for ⁶⁸ Ga-NOTA-3P-TATE-RGD than for ⁶⁸ Ga-DOTATATE (27.2 ± 13.6 vs. 19.5 ± 10.0, P < 0.001); among them, 9 had ¹⁸F-FDG PET/CT and all were found to be FDG-positive. The remaining 23 patients had significantly higher ⁶⁸ Ga-DOTATATE uptake than ⁶⁸ Ga-NOTA-3P-TATE-RGD uptake (22.3 ± 16.4 vs. 11.9 ± 7.5, P < 0.001); among them, 7 had ¹⁸F-FDG PET/CT and 6 were FDG-negative. Generally, ⁶⁸ Ga-DOTATATE demonstrated higher tumour SUVmax than ⁶⁸ Ga-NOTA-3P-TATE-RGD (20.8 ± 16.0 vs. 14.2 ± 8.9, P < 0.001), including primary tumours, liver lesions, lymph node lesions, and bone lesions. However, the tumour-to-background ratio of liver lesions was significantly higher when using ⁶⁸ Ga-NOTA-3P-TATE-RGD compared with that when using ⁶⁸ Ga-DOTATATE (8.4 ± 5.5 vs. 4.7 ± 3.7, P < 0.001).

Conclusion: ⁶⁸ Ga-NOTA-3P-TATE-RGD performed better than ⁶⁸ Ga-DOTATATE in detection of liver metastases with a higher tumour-to-background ratio. Moreover, ⁶⁸ Ga-NOTA-3P-TATE-RGD tended to demonstrate higher uptake over ⁶⁸ Ga-DOTATATE in FDG-avid NETs.

Trial registration: Dual SSTR2 and Integrin αvβ3 Targeting PET/CT Imaging (NCT02817945, registered 5 November 2018). URL OF REGISTRY: https://clinicaltrials.gov/ct2/show/NCT02817945.

Keywords: 68 Ga-DOTATATE; 68 Ga-NOTA-3P-TATE-RGD; Integrin αVβ3; Neuroendocrine tumour; Somatostatin receptor.