A prospective randomized, double-blind study to evaluate the diagnostic efficacy of ⁶⁸Ga-NODAGA-LM3 and ⁶⁸Ga-DOTA-LM3 in patients with well-differentiated neuroendocrine tumors: compared with ⁶⁸Ga-DOTATATE.

Abstract

The purpose of this study is to evaluate the diagnostic efficacy of ⁶⁸ Ga-NODAGA-LM3 and ⁶⁸ Ga-DOTA-LM3 and compare them with ⁶⁸ Ga-DOTATATE in patients with well-differentiated neuroendocrine tumors. Patients were prospectively recruited and equally randomized into two arms: Arm A, patients would undergo a whole-body ⁶⁸ Ga-NODAGA-LM3 PET/CT scan on the 1st day and ⁶⁸ Ga-DOTATATE PET/CT scan on the 2nd day; Arm B, patients would undergo a whole-body ⁶⁸ Ga-DOTA-LM3 PET/CT scan on the 1st day and ⁶⁸ Ga-DOTATATE PET/CT scan on the 2nd day. Biodistribution in normal organs, lesion detection ability, and tumor uptake were compared between antagonist and agonist in each arm. A total of 40 patients with well-differentiated NETs, 20 in each arm, were recruited in the study. ⁶⁸ Ga-NODAGA-LM3 showed a similar pattern as ⁶⁸ Ga-DOTATATE, while ⁶⁸ Ga-DOTA-LM3 demonstrated significantly lower uptake in almost all normal organs compared to ⁶⁸ Ga-DOTATATE. Both ⁶⁸ Ga-NODAGA-LM3 and ⁶⁸ Ga-DOTA-LM3 showed superiority in lesion detection compared to ⁶⁸ Ga-DOTATATE on lesion-based and patient-based comparison. ⁶⁸ Ga-NODAGA-LM3 showed a significantly higher tumor uptake (median SUVmax 29.1 versus 21.6, P < 0.05) and tumor-to-background ratio (median tumor-to-liver ratio 5.0 versus 2.9, P < 0.05) compared to ⁶⁸ Ga-DOTATATE. ⁶⁸ Ga-DOTA-LM3 showed comparable uptake (median SUVmax 16.1 versus 17.8, P = 0.714) and higher tumor-to-background ratio (median tumor-to-liver ratio 5.2 versus 2.1, P < 0.05). Both ⁶⁸ Ga-NODAGA-LM3 and ⁶⁸ Ga-DOTA-LM3 are promising SSTR2 antagonists for neuroendocrine tumors. They demonstrated superiority in diagnostic efficacy compared to agonist ⁶⁸ Ga-DOTATATE. ClinicalTrials.gov identifier: NCT04318561.