Semiquantitative SSTR PET metrics show molecular–morphologic discordance after 177Lu-DOTATATE in gastroenteropancreatic neuroendocrine neoplasms: an exploratory paired target-lesion analysis

Abstract Objective To assess whether simple paired semiquantitative somatostatin receptor (SSTR) PET metrics identify treatment-related changes after 177Lu-DOTATATE in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and to explore their relationship with single-lesion size measured on contrast-enhanced CT in an exploratory paired target-lesion framework. Methods We retrospectively evaluated 29 consecutive patients with GEP-NENs who completed four cycles of 177Lu-DOTATATE and underwent baseline and post-treatment 68Ga-DOTA-peptide PET/CT. Median age at treatment initiation was 64.5 years, 18/29 patients were male, 15 had a pancreatic primary, 13 an intestinal primary, and 1 a pancreatic/duodenal primary of uncertain origin. Most tumors were grade 2 (17/29), and liver metastases were present in 26/29 patients. For each patient, semiquantitative measurements were extracted from the target lesion recorded in the institutional database at baseline and post-treatment assessment. SUVmax, SUVmean, target lesion size, Krenning score, tumor-to-liver ratio, and tumor-to-blood ratio were compared between baseline and post-treatment imaging. Exploratory molecular response was defined as a reduction of at least 30% in semiquantitative PET parameters, whereas exploratory morphologic change was defined as a reduction of at least 20% in lesion size measured on contrast-enhanced CT. Baseline PET/CT was typically performed within 4–6 weeks before PRRT initiation, and post-treatment PET/CT approximately 3 months after PRRT completion according to institutional routine practice. Results Median target lesion SUVmax decreased from 52.22 to 29.73 ( p = 0.0007), and median SUVmean decreased from 11.44 to 7.25 ( p = 0.023). Median target lesion size changed from 2.80 to 2.49 cm and was not significantly different ( p = 0.168). Tumor-to-liver ratio decreased from 9.38 to 5.31 ( p < 0.001), and tumor-to-blood ratio from 45.96 to 22.57 ( p < 0.001). Krenning score showed a modest but significant shift despite an unchanged median value of 4 ( p = 0.0049). Using predefined exploratory thresholds, molecular response based on tumor-to-blood ratio was observed in 20/29 patients, whereas exploratory contrast-enhanced CT-based size reduction was observed in 9/29; 14 of 20 patients with molecular response showed no concomitant size reduction. Among 24 patients with evaluable final imaging response, a tumor-to-blood ratio reduction of at least 30% was observed in 10/11 patients with complete or partial response and in 7/13 with stable or progressive disease. Conclusions In this exploratory paired target-lesion analysis, semiquantitative SSTR PET metrics showed significant treatment-related changes after 177Lu-DOTATATE, whereas paired single-lesion size changes on contrast-enhanced CT were modest. These findings support the presence of molecular–morphologic discordance after PRRT and suggest that normalized PET-derived metrics deserve further investigation as practical tools for post-treatment assessment in GEP-NENs.