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

BMC Cancer. 2021 Aug 25;21(1):950. doi: 10.1186/s12885-021-08551-8.


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. 177Lu-octreotate is routinely administered for treatment of neuroendocrine tumors overexpressing somatostatin receptors (SSTR). The aim of this study was to examine the biodistribution of 177Lu-octreotate in mice bearing aggressive human NB cell lines, in order to evaluate the potential usefulness of 177Lu-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 177Lu-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 177Lu 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 177Lu-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 177Lu-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 177Lu-octreotate as a therapeutic alternative for metastatic NB.

Keywords: 177Lu-DOTATATE; Lutathera; Neuroendocrine tumor; Peptide receptor radionuclide therapy; Somatostatin receptors.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Female
  • Humans
  • Lutetium / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Neuroblastoma / radiotherapy*
  • Octreotide / analogs & derivatives*
  • Radioisotopes / therapeutic use*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Radioisotopes
  • Lutetium
  • Lutetium-177
  • Octreotide