Assessment of the diagnostic efficacy and clinical significance of [18F]AlF-NOTA-LM3 PET/CT in patients with well-differentiated neuroendocrine tumors.

PURPOSE: This study aimed to compare the diagnostic efficacy and clinical management impact of [18F]AlF-NOTA-LM3 with [68Ga]Ga-DOTATATE or [68Ga]Ga-NODAGA-LM3 in patients with well-differentiated neuroendocrine tumors.

METHODS

Patients with histologically confirmed well-differentiated NETs were prospectively recruited and randomized into two arms: Arm A, undergo [18F]AlF-NOTA-LM3 and [68Ga]Ga-DOTATATE PET/CT; Arm B, undergo [18F]AlF-NOTA-LM3 and [68Ga]Ga-NODAGA-LM3 PET/CT. Biodistribution, lesion numbers, and lesion uptake were compared. The impact on clinical management was evaluated. Additionally, a post-hoc analysis of the sensitivity of [18F]AlF-NOTA-LM3 and 68Ga-labeled tracers was evaluated.

RESULTS

A total of 78 patients were included in this study: 38 in Arm A and 40 in Arm B. [18F]AlF-NOTA-LM3 showed lower abdominal organ uptake than [68Ga]Ga-DOTATATE and [68Ga]Ga-NODAGA-LM3. [18F]AlF-NOTA-LM3 was superior to [68Ga]Ga-DOTATATE in liver (684 vs. 449, P<0.001) and lymph node lesion (41 vs. 29, P = 0.005) detection, and superior to [68Ga]Ga-NODAGA-LM3 in liver lesion (625 vs. 490, P = 0.001) detection. The lesion-level sensitivity of [18F]AlF-NOTA-LM3 was significantly higher than that of [68Ga]Ga-DOTATATE (90.6% vs. 67.6%, P<0.001) and [68Ga]Ga-NODAGA-LM3 (90.9% vs. 81.0%, P<0.001), particularly for liver metastases. [18F]AlF-NOTA-LM3 led to a clinical management change in 18.5% (7/38) of patients in Arm A and 12.5% (5/40) of patients in Arm B: 13.2% (5/38) in Arm A and 7.5% (3/40) in Arm B with major changes, while 5.3% (2/38) in Arm A and 5% (2/40) in Arm B with minor changes.

CONCLUSION

[18F]AlF-NOTA-LM3 shows superior diagnostic efficacy than [68Ga]Ga-DOTATATE and [68Ga]Ga-NODAGA-LM3. [18F]AlF-NOTA-LM3 demonstrates significant value in guiding clinical decision-making in a subgroup of patients.

TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06056362.