Neuroendocrine tumors (NETs) can be treated by peptide receptor radionuclide therapy using radiolabeled somatostatin analogs. However, the efficacy of such treatment is low and needs to be optimized. Our study evaluated the potential radiosensitizing effects of inhibition of nicotineamide phosphoribosyltransferase on ¹⁷⁷Lu-DOTATATE treatment in a NET model. Methods: Nude mice xenografted with the human NET cell line GOT1 were treated with semiefficient doses of ¹⁷⁷Lu-DOTATATE (7.5 MBq, intravenously) or the nicotineamide phosphoribosyltransferase inhibitor GMX1778 (100 mg/kg/wk, orally). Results: Median time to tumor progression (tumor volume larger than at day 0) was 3 d for controls, 7 d for single-dose GMX1778, 28 d for single-dose ¹⁷⁷Lu-DOTATATE, 35 d for 3 weekly doses of GMX1778, and 98 d for combined treatment with ¹⁷⁷Lu-DOTATATE and GMX1778 × 1. After ¹⁷⁷Lu-DOTATATE and 3 weekly doses of GMX1778, none of the tumors progressed within 120 d. Conclusion: GMX1778 enhances the efficacy of ¹⁷⁷Lu-DOTATATE treatment and induces a prolonged antitumor response.

Radioembolization (RE) with intra-arterial administration of ⁹⁰Y microspheres is a promising technique for the treatment of liver metastases from small intestinal neuroendocrine tumors (SI-NET) not amenable to surgery or local ablation. However, studies comparing RE to other loco-regional therapies are lacking. The aim of this randomized study was to compare the therapeutic response and safety after RE and bland hepatic arterial embolization (HAE), and to investigate early therapy-induced changes with diffusion-weighted MRI (DWI-MRI).

(1) Purpose: Small intestinal neuroendocrine tumors (SI-NETs) often present with distant metastases at diagnosis. Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a systemic treatment that increases overall survival (OS) in SI-NET patients with stage IV disease. However, the treatment response after PRRT, which targets somatostatin receptor 2 (SSTR2), is variable and predictive factors have not been established. This exploratory study aims to evaluate if SSTR2 expression in SI-NETs could be used to predict OS after PRRT treatment. (2) Methods: Using a previously constructed Tissue Micro Array (TMA) we identified tissue samples from 42 patients that had received PRRT treatment during 2006–2017 at Sahlgrenska University hospital. Immunohistochemical expression of SSTR2, Ki-67 and neuroendocrine markers synaptophysin and Chromogranin A (CgA) were assessed. A retrospective estimation of ¹⁷⁷Lu-DOTATATE uptake in 33 patients was performed. Data regarding OS and non-surgical treatment after PRRT were collected. Another subgroup of 34 patients with paired samples from 3 tumor sites (primary tumor, lymph node and liver metastases) was identified in the TMA. The SSTR2 expression was assessed in corresponding tissue samples (n = 102). (3) Results: The patients were grouped into Low SSTR2 or High SSTR2 groups based upon on levels of SSTR2 expression. There was no significant difference in ¹⁷⁷Lu-DOTATATE uptake between the groups. The patients in the Low SSTR2 group had significantly longer OS after PRRT than the patients in the High SSTR2 group (p = 0.049). PRRT treated patients with low SSTR2 expression received less additional treatment compared with patients with high SSTR2 expression. SSTR2 expression did not vary between tumor sites but correlated within patients. (4) Conclusion: The results from the present study suggest that retrospective evaluation of SSTR2 expression in resected tumors cannot be used to predict OS after PRRT.

Purpose Small intestinal neuroendocrine tumours (SI-NET) often present with distant metastases at diagnosis. Peptide receptor radiotherapy (PRRT) with radiolabelled somatostatin analogues is a systemic treatment that increases overall survival (OS) in patients with SI-NET. However, PRRT treatment response is variable and predictive factors have not been established. PRRT predominantly targets somatostatin receptor 2 (SSTR2). This study evaluates if SSTR2 expression in SI-NET tumours predicts OS after PRRT treatment.Methods Using a previously constructed Tissue Micro Array (TMA) consisting of 412 SI-NET patients we identified a subgroup consisting of 44 patients (95 tissue samples) that had received PRRT treatment during 2006-2016 at Sahlgrenska University hospital. IHC expression of SSTR2, Ki-67 and neuroendocrine markers were assessed. A retrospective estimation of 177 Lu-DOTATATE uptake in 33 patients was performed. An additional subgroup of 34 patients with paired samples from 3 tumour sites was identified. SSTR2 expression was assessed in corresponding tissue samples (n=102). Data regarding OS and non-surgical treatment were collected for both groups.Results SSTR2 expression did not vary between tumour sites but correlated among the patients’ lesions. Patients were grouped into Low SSTR2 or High SSTR2 depending on levels of SSTR2 expression. OS based on SSTR2 expression was not significantly different. However, PRRT treated patients with low SSTR2 expression received less additional treatment compared to patients with high SSTR2 expression and had a tendency towards higher 177 Lu-DOTATATE uptake.Conclusion The results from the present study suggest that low SSTR2 expression should not exclude patients from PRRT.