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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.

Purpose: To develop a care process model for the delivery of peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-Dotatate for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods: A multidisciplinary, structured PRRT process model was established. Over the last 9 months, meetings were held bi-weekly to discuss the logistics of clinical trials. Meetings are still held regularly at the Mayo Clinic Florida to discuss plans regarding commercially available PRRT treatments. The process model has evolved as we have treated patients on both clinical trials and commercial treatments. Results: An effective process model was formulated. We had 5 patients on our Expanded Access Program (EAP) clinical trial. Our ability to be a part of the EAP allowed us to understand the mechanics of how to treat these patients, and what was involved before it became commercially available. Since commercial availability of the 177Lu-Dotatate, more than 50 treatments (>20 patients) have already been completed, with several new patients getting started on treatment every week. Our nuclear medicine department receives continual requests to schedule new patients for PRRT. This can be attributed to our streamlined approach in delivering PRRT to our patients. Conclusion: A thorough procedural approach was formulated to provide patients with PRRT. Experiences and challenges led to refinement, which has allowed the process to advance. This development could lead to better patient outcomes, treatment efficiency, and a reference standard for other institutions trying to develop this at their location.