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Better therapeutic results after fractionated administration of Lu-177-octreotate in mice bearing human neuroblastoma

Authors Arman Romiani
Johan Spetz
Emman Shubbar
Ruth H. Palmer
Bengt Hallberg
Eva Forssell-Aronsson
Published in The European Association of Nuclear Medicine (EANM)
Publication year 2018
Published at Institute of Clinical Sciences, Department of Radiation Physics
Sahlgrenska Cancer Center
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Language en
Subject categories Laboratory animal science, Cell biology, Cancer and Oncology


Background: Neuroblastoma (NB) is a neuroendocrine tumor and one of the most common cancer types in infants. NB is a heterogeneous cancer form, meaning that it has various characteristics and features, with diverse outcomes. High-risk NB has a 5-year survival rate of only 40-50%, demonstrating the need for new and improved treatment options for this patient group. Since NB overexpresses somatostatin receptors Lu-177-octreotate has the potential to be a treatment option. Our previous in vitro studies indicated high and specific uptake of Lu-177-octreotate in the human NB cell lines CLB-Bar and IMR-32. Furthermore, biodistribution studies of Lu-177-octreotate in NB-xenografted mice showed high uptake in tumor tissue in comparison with risk organs. These promising results encouraged studies on the anti-tumor effects of Lu-177-octreotate therapy. The aim of this work was to study the anti-tumor effects after fractionated administration of Lu-177-octreotate in nude mice bearing CLB-Bar. Methods: Nude BALB/c mice aged 5-6 weeks were injected with 2x10^6 CLB-Bar cells on the flank of the mice. Mice with tumors between 250 and 1100 mm^3 were included in the study. Three groups of mice were i.v injected with totally 15 MBq Lu-177-octreotate: given as 15 MBq x1, 7.5 MBq x2 with a 2-h interval or 5 MBq x3 with 1-h interval. The tumor volume was measured with a caliper twice a week after injection and the mice were killed when the tumor mass exceeded 10 % of the body weight. Results: The relative tumor volume 7 days post injection was 2.0, 1.7 and 1.3 for the 15 MBq x1, 7.5 MBq x2 and 5 MBq x3 group, respectively, corresponding mean survival time after study start was of 9.6, 14 and 16 days, respectively. Conclusion: The fractionated administration of Lu-177-octreotate resulted in a better anti-tumor effect, with the most prominent results from 3x5 MBq. These results might be due to saturation of the somatostatin receptors for the higher amounts of Lu-177-octreotate or upregulation of receptors from previous fractions. Further studies are needed to optimize the fractionation scheme and to evaluate the mechanisms behind the results.

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