Histologic Ex Vivo Validation of the [¹⁸F]SITATE Somatostatin Receptor PET Tracer

Abstract

Radiolabeled somatostatin analogs (SSAs), such as [⁶⁸Ga]Ga-DOTA SSAs, have transformed imaging and therapeutic strategies. However, their use is constrained by the high cost of generators and their short half-life. In contrast, [¹⁸F]SITATE presents a promising alternative, offering the advantage of a longer half-life than ⁶⁸Ga, along with the cost-effectiveness of cyclotron-based production. This study evaluated the first histologic ex vivo validation of [¹⁸F]SITATE. Methods: This study retrospectively included 47 patients (57% male; mean age, 66.9 ± 14.9 y) with histologically confirmed well-differentiated neuroendocrine neoplasms who underwent [¹⁸F]SITATE PET followed by surgery within 4 mo. Lesion uptake was quantified using SUV_mean, SUV_peak, SUV_max, and tumor-to-liver ratio (TLR). Histologic somatostatin receptor (SSTR) type 2 expression was determined using histological scores (H-scores), with thresholds defining SSTR scores 1–3. The accuracy of PET imaging for preoperative metastatic detection was evaluated against surgical histology. Results: PET imaging demonstrated a significant correlation between [¹⁸F]SITATE uptake (SUV_mean and TLR) and SSTR type 2 H-scores (r = 0.618 and 0.622, respectively; P < 0.0001). SSTR score 3 correlated with increased SUV_mean and TLR (P < 0.0001). Among 35 patients with primary resection and lymphadenectomy, PET achieved a sensitivity of 73.9% and specificity of 100%. Conclusion: [¹⁸F]SITATE PET imaging strongly correlates with histologic SSTR expression, demonstrating utility in staging and guiding therapeutic decisions in neuroendocrine neoplasms. This ¹⁸F-labeled tracer shows specificity comparable to historical [⁶⁸Ga]Ga-DOTA SSA data, whereas an increase in sensitivity for the detection of locoregional metastases appears possible. Further head-to-head comparisons of [¹⁸F]SITATE with traditional [⁶⁸Ga]Ga-DOTA SSA and histologic validation are warranted to optimize its diagnostic accuracy and clinical impact.