Association between SSTR2 expression and [68Ga]Ga-DOTATOC PET/CT uptake in neuroblastoma: A retrospective analysis

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Purpose The somatostatin receptor subtype 2 (SSTR2) is highly expressed in neuroblastoma, a malignant paediatric solid tumour arising from the neural crest. This receptor plays an important role in both diagnostics (imaging with [ 68 Ga]Ga-DOTATOC scans) and therapy ([ 177 Lu]Lu-DOTATATE). Understanding the extent of SSTR2 expression is critical to evaluate the potential of these theranostics for neuroblastoma. Methods We retrospectively included patients with neuroblastoma who underwent [ 68 Ga]Ga-DOTATOC PET/CT and had corresponding tumour tissue available for SSTR2 immunohistochemistry (IHC) between 2016 and 2025. IHC was assessed for SSTR2 expression and quantified by H-score, categorised as negative, weak, moderate or strong. [ 68 Ga]Ga-DOTATOC PET/CT uptake was quantified using SUV max and SUV peak in tumour volume of interests (VOI). Statistical analysis included Spearman's rank. correlation, Kruskal-Wallis test, and linear regression. Changes in H-score over time were evaluated in patients with multiple tissue samples. Results Seventeen patients met the inclusion criteria. Higher H-scores correlated significantly with greater [ 68 Ga]Ga-DOTATOC PET/CT uptake (SUV peak ) (Spearman's ρ = 0.667, p = 0.0034). [ 68 Ga]Ga-DOTATOC uptake differed significantly across the strong and negative ( p < 0.01) or weak/moderate ( p < 0.05) SSTR2 expression groups. Linear regression revealed a significant positive association between H-score and SUV peak (β = 0.042; 95 % CI: 0.016–0.068; p = 0.0034), accounting for approximately 45 % of the variance in SUV peak values (R 2 = 0.45). SSTR2 expression over time showed intra- and inter-patient heterogeneity. Conclusion This study showed a statistically significant association between SSTR2 expression and [ 68 Ga]Ga-DOTATOC PET/CT uptake in neuroblastoma. The heterogeneity in SSTR expression supports the need for personalised treatment and imaging strategies, in which H-score may serve as a useful biomarker to guide patient selection for [ 68 Ga]Ga-DOTATOC PET/CT and SSTR2-targeted therapy. Prospective studies in larger cohorts are warranted to confirm these findings.

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