Comparison of 177Lu-octreotate and 177Lu-octreotide for treatment in human neuroblastoma-bearing mice

Background: Patients with high -risk neuroblastoma (NB) have a 5 -year event -free survival of less than 50 %, and novel and improved treatment options are needed. Radiolabeled somatostatin analogs (SSTAs) could be a treatment option. The aims of this work were to compare the biodistribution and the therapeutic effects of 177 Lu-octreotate and 177 Lu-octreotide in mice bearing the human CLB-BAR NB cell line, and to evaluate their regulatory effects on apoptosis-related genes. Methods: The biodistribution of 177 Lu-octreotide in mice bearing CLB-BAR tumors was studied at 1, 24, and 168 h after administration, and the absorbed dose was estimated to tumor and normal tissues. Further, animals were administered different amounts of 177 Lu-octreotate or 177 Lu- octreotide. Tumor volume was measured over time and compared to a control group given saline. RNA was extracted from tumors, and the expression of 84 selected genes involved in apoptosis was quantified with qPCR. Results: The activity concentration was generally lower in most tissues for 177 Lu-octreotide compared to 177 Lu-octreotate. Mean absorbed dose per administered activity to tumor after injection of 1.5 MBq and 15 MBq was 0.74 and 0.03 Gy/MBq for 177 Lu-octreotide and 2.9 and 0.45 Gy/MBq for 177 Lu-octreotate, respectively. 177 Lu-octreotide treatment resulted in statistically significant differences compared to controls. Fractionated administration led to a higher survival fraction than after a single administration. The pro-apoptotic genes TNSFS8 , TNSFS10 , and TRADD were regulated after administration with 177 Lu-octreotate. Treatment with 177 Lu- octreotide yielded regulation of the pro-apoptotic genes CASP5 and TRADD , and of the antiapoptotic gene IL10 as well as the apoptosis-related gene TNF . Conclusion: 177 Lu-octreotide gave somewhat better anti -tumor effects than 177 Lu-octreotate. The similar effect observed in the treated groups with 177 Lu-octreotate suggests saturation of the somatostatin receptors. Pronounced anti -tumor effects following fractionated administration merited receptor saturation as an explanation. The gene expression analyses suggest apoptosis activation through the extrinsic pathway for both radiopharmaceuticals.