The impact of injected peptide mass on small intestinal neuroendocrine tumor and normal organ somatostatin receptor expression; Measurements on 68Ga-DOTATOC-PET in a simulated therapy setting

Abstract Background The impact of systemic somatostatin analogs on tumor versus normal organ somatostatin receptors (SSR) in conjunction with peptide receptor radionuclide therapy (PRRT) has long been debated. In a previous 68 Ga-DOTATOC-PET/CT study, at 7 h post intravenous (iv) injection of a preload of 400 µg octreotide, the SSR expression in small intestinal neuroendocrine tumors was restored to baseline levels, but remained reduced by approximately 50% in liver, spleen and pancreas creating a “therapeutic window”. The present study explored this “window” in a simulated PRRT setting in patients with disseminated Si-NETs, by firstly administer the 400 µg iv octreotide preload, and secondly 150 µg of iv octreotide at 68 Ga-DOTATOC-PET/CT, to identify possible organ protection and tumor response difference in all, large and small tumors. Methods Nine patients underwent three serial 68 Ga-DOTATOC-PET/CT examinations during two days, including both dynamic and static whole-body (WB) registrations. Each PET/CT session started with iv injection of 153 ± 30 MBq, 22.1 ± 6.7 µg (mean ± SD) 68 Ga-DOTATOC. Ten minutes before the last two PET/CT sessions, an extra iv infusion of 150 µg octreotide was administered, and five hours prior to the last PET/CT, an iv infusion of 400 µg octreotide was given. Measurements were performed of tumor uptake (mean SUV) and net influx rate (K i ), as well as SUV (mean) in abdominal organs blood and bone marrow (BM), utilized 50% iso-contour volumes of interest. Results Over time, SUV and K i in Si-NETs declined in parallel with rising peptide concentrations (p < 0.05) for the groups of all- and small tumors while the large tumor group showed no decline. A decline in SUV (30–50%) was observed in the abdominal organs at the second PET/CT scan (WB 2) (p < 0.004), performed in conjunction with 150 µg of iv octreotide, and the uptake in spleen and liver decreased further at the third PET/CT scan (WB 3) (p < 0.05). Conclusion In the presence of peptide amounts similar to those administered at PRRT, Si-NET uptake might be reduced more in small than in large tumors cancelling the potential therapeutic benefits of a 400 µg iv octreotide preload. Trial registration Regional Ethics Comitté, Uppsala, Sweden, No. 2014/39. Registered 4 June 2018, https//etikprovningsmyndigheten.se/