Comparison of Lu-octreotate and Lu-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 Lu-octreotate and 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 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 Lu-octreotate or 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 Lu-octreotide compared to 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 Lu-octreotide and 2.9 and 0.45 Gy/MBq for Lu-octreotate, respectively. 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 , , and were regulated after administration with Lu-octreotate. Treatment with Lu-octreotide yielded regulation of the pro-apoptotic genes and , and of the anti-apoptotic gene as well as the apoptosis-related gene .

CONCLUSION

Lu-octreotide gave somewhat better anti-tumor effects than Lu-octreotate. The similar effect observed in the treated groups with 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.