Journal Article

Neuroblastoma xenograft models demonstrate the therapeutic potential of 177Lu-octreotate

Shubbar, Emman, Spetz, Johan, Palmer, Ruth H., Forssell-Aronsson, Eva, Romiani, Arman, Hallberg, Bengt, Lind, Dan E.

2021

Overview

Background Neuroblastoma (NB) is one of the most frequently diagnosed tumors in infants. NB is a neuroendocrine tumor type with various characteristics and features, and with diverse outcome. The most malignant NBs have a 5-year survival rate of only 40–50%, indicating the need for novel and improved treatment options. 177 Lu-octreotate is routinely administered for treatment of neuroendocrine tumors overexpressing somatostatin receptors (SSTR). The aim of this study was to examine the biodistribution of 177 Lu-octreotate in mice bearing aggressive human NB cell lines, in order to evaluate the potential usefulness of 177 Lu-octreotate for treatment of NB. Methods BALB/c nude mice bearing CLB-BAR, CLB-GE or IMR-32 tumor xenografts ( n  = 5–7/group) were i.v. injected with 0.15 MBq, 1.5 MBq or 15 MBq 177 Lu-octreotate and sacrificed 1 h, 24 h, 48 h and 168 h after administration. The radioactivity concentration was determined for collected tissue samples, tumor-to-normal-tissue activity concentration ratios (T/N) and mean absorbed dose for each tissue were calculated. Immunohistochemical (IHC) staining for SSTR1–5, and Ki67 were carried out for tumor xenografts from the three cell lines. Results High 177 Lu concentration levels and T/N values were observed in all NB tumors, with the highest for CLB-GE tumor xenografts (72%IA/g 24 h p.i.; 1.5 MBq 177 Lu-octreotate). The mean absorbed dose to the tumor was 6.8 Gy, 54 Gy and 29 Gy for CLB-BAR, CLB-GE and IMR-32, respectively, p.i. of 15 MBq 177 Lu-octreotate. Receptor saturation was clearly observed in CLB-BAR, resulting in higher concentration levels in the tumor when lower activity levels where administered. IHC staining demonstrated highest expression of SSTR2 in CLB-GE, followed by CLB-BAR and IMR-32. Conclusion T/N values for all three human NB tumor xenograft types investigated were high relative to previously investigated neuroendocrine tumor types. The results indicate a clear potential of 177 Lu-octreotate as a therapeutic alternative for metastatic NB.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 177Lu-DOTATATE / Biodistribution / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cancer therapies / Care and treatment / Chemotherapy / Chromatography / Diagnosis / Experiments / Health Promotion and Disease Prevention / Lutathera / Medical prognosis / Medicine/Public Health / Metastases / Metastasis / Mutation / Neuroblastoma / Neuroendocrine tumor / Neuroendocrine tumors / Oncology / Peptide receptor radionuclide therapy / Radiation / Radioactivity / Somatostatin / Somatostatin receptors / Surgery / Surgical Oncology / Tumors / Xenografts / Xenotransplantation