Head-to-Head Comparison of SSTR Antagonist [ 68 Ga]Ga-DATA 5m -LM4 with SSTR Agonist [ 68 Ga]Ga-DOTANOC PET/CT in Patients with Well Differentiated Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Imaging Study

Neuroendocrine tumors (NETs) are slow-growing tumors that express high levels of somatostatin receptors (SSTRs). Recent studies have shown the superiority of radiolabeled SSTR antagonists in theranostics compared to agonists. In this prospective study, we compared the diagnostic efficacy between [ 68 Ga]Ga-DOTANOC and [ 68 Ga]Ga-DATA 5m -LM4 in the detection of primary and metastatic lesions in patients with well differentiated gastroenteropancreatic (GEP) NETs. Histologically proven GEP-NET patients underwent [ 68 Ga]Ga-DOTANOC & [ 68 Ga]Ga-DATA 5m -LM4 PET/CT scans, which were analyzed. The qualitative analysis involved the visual judgment of radiotracer uptake validated by the morphological findings using CT, which was considered as the reference standard. Quantitative comparisons were presented as the standardized uptake value (SUV) corrected for lean body mass: SULpeak, SULavg, and tumor-to-background ratios (TBR). In total, 490 lesions were confirmed via diagnostic CT. The lesion-based sensitivity of [ 68 Ga]Ga-DATA 5m -LM4 PET/CT was 94.28% (462/490) and 83.46% (409/490) for [ 68 Ga]Ga-DOTANOC PET/CT ( p < 0.0001). [ 68 Ga]Ga-DATA 5m -LM4 had statistical significance over [ 68 Ga]Ga-DOTANOC in liver metastases [100% vs. 89.4%; p < 0.0001 (292 vs. 253 {283 lesions on CT})] and bone metastases [100% vs. 82.9%; p = 0.005 (45 vs. 34 {41 lesions on CT})]. Statistical significance was also noted for the TBR SULpeak of the primary and liver lesions. [ 68 Ga]Ga-DATA 5m -LM4 showed better sensitivity and a higher target-to-background ratio than [ 68 Ga]Ga-DOTANOC PET/CT. [ 68 Ga]Ga-DATA 5m -LM4 PET/CT can be used to quantify the extent of skeletal and liver metastases for better planning of SSTR agonist- or antagonist-based therapy.