The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [(177)Lu]-DOTATATE

AIM: Purpose of this study was to evaluate the association of the spatial heterogeneity (asphericity, ASP) in intra-therapeutic SPECT/ CT imaging of somatostatin receptor (SSR) positive metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) for morphological treatment response to peptide receptor radionuclide therapy (PRRT). Secondly, we correlated ASP derived form a pre-therapeutic OctreoScan (ASP([In])) and an intra-therapeutic [(177)Lu]-SPECT/CT (ASP([Lu])). MATERIALS AND METHODS: Data from first therapy cycle [(177)Lu-DOTA(0)-Tyr(3)]octreotate ([(177)Lu]-DOTATATE)-PRRT was retrospectively analyzed in 33 patients (m = 20; w = 13; median age, 72 [46–88] years). The evaluation of response to PRRT was performed according to RECIST 1.1 in responding lesions [RL (SD, PR, CR), n = 104] and non-responding lesions [NRL (PD), n = 27]. The association of SSR tumor heterogeneity with morphological response was evaluated by Kruskal-Wallis test and receiver operating characteristic curve (ROC). The optimal threshold for separation (RL vs. NRL) was calculated using the Youden-index. Relationship between pre- and intra-therapeutic ASP was determined with Spearman’s rank correlation coefficient (ρ) and Bland-Altman plots. RESULTS: A total of 131 lesions (liver: n = 59, lymph nodes: n = 48, bone: n = 19, pancreas: n = 5) were analyzed. Lesions with higher ASP values showed a significantly poorer response to PRRT (PD, median: 11.3, IQR: 8.5–15.5; SD, median: 3.4, IQR: 2.1–4.5; PR, median 1.7, IQR: 0.9–2.8; CR, median: 0.5, IQR: 0.0–1.3); Kruskal-Wallis, p<0.001). ROC analyses revealed a significant separation between RL and NRL for ASP after 4 months (AUC 0.85, p<0.001) and after 12 months (AUC 0.94, p<0.001). The optimal threshold for ASP was >5.45% (sensitivity 96% and specificity 82%). The correlation coefficient of pre- and intra-therapeutic ASP revealed ρ = 0.72 (p <0.01). The mean absolute difference between ASP([In]) and ASP([Lu]) was -0.04 (95% Limits of Agreement, -6.1–6.0). CONCLUSION: Pre- and intra-therapeutic ASP shows a strong correlation and might be an useful tool for therapy monitoring.