SSTR-Targeted Radiotheranostics in Breast Cancer: A Comparison of [⁶⁸Ga]Ga-DOTATOC and [⁶⁸Ga]Ga-SSO120 with [¹⁸F]FDG PET.

Abstract

Somatostatin receptor (SSTR)-targeting radiotracers hold promise for theranostic applications in breast cancer (BC). This retrospective single-center study aimed to assess the proportion of SSTR-positive BC and its relevance for peptide receptor radionuclide therapy. SSTR-agonist- and SSTR-antagonist-based PET tracers are compared. <b>Methods:</b> Patients with BC who underwent PET imaging with SSTR agonist [⁶⁸Ga]Ga-DOTATOC or SSTR antagonist [⁶⁸Ga]Ga-SSO120 (February 2023 to February 2025) for initial or follow-up staging were included. All patients underwent [¹⁸F]FDG PET, which was used as the reference standard. Mean administered activities and uptake times were 88 MBq for 64 min with [⁶⁸Ga]Ga-DOTATOC and 131 MBq for 66 min with [⁶⁸Ga]Ga-SSO120, respectively. PET-positive lesions were reported in 6 anatomic categories. Tumors were segmented; SUVs, tumor-to-liver ratios, and tumor volumes were calculated. Time to progression stratified by SSTR expression was assessed using the log-rank test. <b>Results:</b> In total, 37 patients with BC (26 estrogen-receptor [ER]-positive, 11 triple negative [TN]) were identified; final analysis was limited to 30 patients after excluding 7 with no detectable tumor. Most had metastatic disease (M1) at staging (26/36). On the patient level, SSTR-positive tumor (≥1 lesion) was detected in 80% of ER-positive BC (16/20) and in 50% of patients with TNBC (5/10). In ER-positive disease, positivity was comparable for [⁶⁸Ga]Ga-DOTATOC (85%) and [⁶⁸Ga]Ga-SSO120 (71%), whereas in TNBC, positivity was observed with [⁶⁸Ga]Ga-DOTATOC (83%) only. On the region level, 60% (31/52) of [¹⁸F]FDG-positive regions in ER-positive BC and 33% (7/21) in TNBC were SSTR-positive. Region-based mean SUV_max was generally lower with SSTR imaging: 7.2 ± 3.4 versus 9.3 ± 4.3 ([⁶⁸Ga]Ga-DOTATOC vs. [¹⁸F]FDG) and 4.5 ± 1.4 versus 8.1 ± 3.2 ([⁶⁸Ga]Ga-SSO120 vs. [¹⁸F]FDG) in ER-positive BC and 4.1 ± 0.6 versus 19.8 ± 3.3 ([⁶⁸Ga]Ga-DOTATOC vs. [¹⁸F]FDG), with absent [⁶⁸Ga]Ga-SSO120 uptake in patients with TNBC. One patient reached a Krenning score of 3, indicating technical eligibility for peptide receptor radionuclide therapy. SSTR positivity did not correlate with time to progression. <b>Conclusion:</b> SSTR may serve as a promising radiotheranostic target in a small subset of patients with advanced metastatic ER-positive BC. Tumor uptake was mostly moderate, without substantial difference between [⁶⁸Ga]Ga-DOTATOC and [⁶⁸Ga]Ga-SSO120. For imaging, [¹⁸F]FDG PET outperformed [⁶⁸Ga]Ga-SSTR PET in patients with ER-positive BC and TNBC.