Theranostics with somatostatin receptor antagonists in SCLC: Correlation of Ga-SSO120 PET with immunohistochemistry and survival.

Positron Emission Tomography (PET) using the somatostatin receptor 2 (SSTR2)-antagonist satoreotide trizoxetan (Ga-SSO120) is a novel, promising imaging modality for small-cell lung cancer (SCLC), which holds potential for theranostic applications. This study aims to correlate uptake in PET imaging with SSTR2 expression in immunohistochemistry (IHC) and to assess the prognostic value of Ga-SSO120 PET at initial staging of patients with SCLC. We analyzed patients who underwent Ga-SSO120 PET/CT during initial diagnostic workup of SCLC as part of institutional standard-of-care. SSTR2 expression in IHC was evaluated on a 4-level scale and correlated with normalized standardized uptake values and tumor-to-liver ratios (SUV and TLR) in Ga-SSO120 PET on a lesion level. Highest lesion SUV/TLR per patient, SSTR2 score in IHC, M status according to TNM classification, and other parameters were analyzed for association with overall survival (OS) and time to treatment failure (TTF) by univariate, multivariate (cut-off values were identified on data for best separation), and stratified Cox regression. We included 54 patients (24 men/30 women, median age 65 years, 21 M0/33 M1 according to TNM classification). In 43 patients with available surplus tumor tissue samples, hottest lesion SUV/TLR showed a significant correlation with the level of SSTR2-expression by tumor cells in IHC (Spearman's rho 0.86/0.81, both p < 0.001; ANOVA p < 0.001). High SSTR2 expression in IHC, Ga-SSO120 SUV and TLR of the hottest lesion per patient, whole-body TLR, MTV, TLG, M status, and serum LDH showed a significant association with inferior TTF/OS in univariate analysis. In separate multivariate Cox regression (including sex, age, M stage, and LDH) higher hottest-lesion TLR showed a significant association with shorter OS (HR = 0.26, 95%CI: 0.08-0.84, p = 0.02) and SSTR2 expression in IHC with significantly shorter TTF (HR = 0.24, 95%CI: 0.08-0.71, p = 0.001) and OS (HR = 0.22, 95%CI: 0.06-0.84, p = 0.03). In total, 12 patients (22.2%) showed low (< 1), 21 (38.9%) intermediate (≥ 1 but < 2), 14 (25.9%) high (≥ 2 but < 5), and 7 (13.0%) very high (≥ 5) whole-body mean TLR. In patients with SCLC, SSTR2 expression assessed by Ga-SSO120 PET and by IHC were closely correlated and associated with shorter survival. More than 75% of patients showed higher whole-body Ga-SSO120 tumor uptake than liver uptake and almost 40% high or very high uptake, possibly paving the way towards theranostic applications.