Impact of antagonist peptides and chelators on the diagnostic performance of PET/CT using gallium-68–labeled somatostatin receptor antagonists

Objective: Different SSTR2 antagonists have been developed. This study aims to evaluate the impact of different peptides and chelators on the diagnostic performance of SSTR2 antagonists in well-differentiated NETs. Methods: In this prospective study, participants were equally randomized into 2 arms: arm A, participants would undergo a whole-body 68Ga-NODAGA-LM3 PET/CT scan on the first day and 68Ga-DOTA-LM3 PET/CT scan on the second day; arm B, participants would undergo a whole-body 68Ga-NODAGA-LM3 PET/CT scan on the first day and 68Ga-NODAGA-JR11 PET/CT scan on the second day. Biodistribution in normal organs, lesion detection ability, and tumor uptakes were compared within each arm. Results: A total of 40 participants (age, 49.5 ± 13.4, 21 men), 20 in each arm, were recruited in the study. In arm A, 68Ga-DOTA-LM3 showed lower background. However, the lesion detection ability (overall lesion detected, 445 vs 548; P = .005) and the lesion uptake (overall lesions SUVmax, 19.8 ± 17.2 vs 35.3 ± 28.8; P < .001) was significantly lower than those of 68Ga-NODAGA-LM3. In arm B, both 68Ga-NODAGA-LM3 and 68Ga-NODAGA-JR11 showed similar biodistribution and lesion uptake (SUVmax, 28.5 ± 23.8 vs 25.0 ± 20.0; P < .001) despite minor differences. The lesion detection ability was the same between these 2 tracers (overall lesion detected, 503 vs 503). Conclusions: The diagnostic performance of SSTR2 antagonists was sensitive to chelators. Both 68Ga-NODAGA-LM3 and 68Ga-NODAGA-JR11 outperformed 68Ga-DOTA-LM3 with higher lesion uptake and detection ability, of which 68Ga-NODAGA-LM3 had marginally but significantly higher lesion uptake.