Gallium-68 labeled somatostatin receptor antagonist PET/CT in over 500 patients with neuroendocrine neoplasms: experience from a single center in China

Purpose: Somatostatin receptor antagonists have shown promising performance for imaging neuroendocrine neoplasms. However, there is a lack of studies exploring the diagnostic performance of SSTR antagonists or comparing them with agonists in a large cohort of patients with NENs. This study aimed to retrospectively review all SSTR antagonist PET/CT scans conducted at Peking Union Medical College Hospital since November 2018 in patients with confirmed or suspected NENs. Methods: Four types of SSTR antagonists were utilized, including [Ga-68]Ga-NODAGA-LM3, [Ga-68]Ga-DOTA-LM3, [Ga-68]Ga-NODAGA-JR11, and [Ga-68]Ga-DOTA-JR11. The reference standard was based on a combination of histopathology, clinical evaluation, imaging results, and follow-up. Patient-based sensitivity, specificity, and accuracy were evaluated. The SUVmax and tumor-to-liver ratio (TLR) of the hottest lesions was recorded and compared between antagonists and [Ga-68]Ga-DOTATATE. Results: A total of 622 antagonist scans from 549 patients were included in the analysis. The patient-level sensitivity, specificity, and accuracy of antagonist imaging (all tracers combined) were 91.0% (443/487), 91.9% (57/62), and 91.1% (500/549), respectively. In 181 patients with a comparative [Ga-68]Ga-DOTATATE PET/CT scan, the patient-level sensitivity, specificity, and accuracy were 87.5% (147/168), 76.9% (10/13), and 86.7% (157/181), respectively. For the hottest lesions, SSTR antagonists all tracers combined demonstrated an overall comparable SUVmax to [Ga-68]Ga-DOTATATE (40.1 +/- 32.5 vs. 39.4 +/- 23.8, p = 0.772). While [Ga-68]Ga-NODAGA-LM3 showed significantly higher uptake than [Ga-68]Ga-DOTATATE (57.4 +/- 38.5 vs. 40.0 +/- 22.8, p<0.001), [Ga-68]Ga-NODAGA-JR11 (39.7 +/- 26.5 vs. 34.3 +/- 23.9, p = 0.108) and [Ga-68]Ga-DOTA-LM3 (38.9 +/- 32.1 vs. 37.2 +/- 22.1, p = 0.858) showed comparable uptake to [Ga-68]Ga-DOTATATE, and [Ga-68]Ga-DOTA-JR11 showed lower uptake (28.9 +/- 26.1 vs. 44.0 +/- 25.7, p = 0.001). All antagonists exhibited significantly higher TLR than [Ga-68]Ga-DOTATATE (12.1 +/- 10.8 vs. 5.2 +/- 4.5, p<0.001). Conclusion: Gallium-68 labeled SSTR antagonists could serve as alternatives to SSTR agonists for imaging of NENs. Among various antagonists, [Ga-68]Ga-NODAGA-LM3 seems to have the best imaging profile.