Internal therapy with α‐emitters should be well suited for micrometastatic disease. Radium‐224 emits multiple α‐particles through its decay and has a convenient 3.6 days of half‐life. Despite its attractive properties, the use of 224Ra has been limited to bone‐seeking applications because it cannot be stably bound to a targeting molecule. Alternative delivery systems for 224Ra are therefore of considerable interest. In this study, calcium carbonate microparticles are proposed as carriers for 224Ra, designed for local therapy of disseminated cancers in cavitary regions, such as peritoneal carcinomatosis. Calcium carbonate microparticles were radiolabeled by precipitation of 224Ra on the particle surface, resulting in high labeling efficiencies for both 224Ra and daughter 212Pb and retention of more than 95% of these nuclides for up to 1 week in vitro. The biodistribution after intraperitoneal administration of the 224Ra‐labeled CaCO3 microparticles in immunodeficient mice revealed that the radioactivity mainly remained in the peritoneal cavity. In addition, the systemic distribution of 224Ra was found to be strongly dependent on the amount of administered microparticles, with a reduced skeletal uptake of 224Ra with increasing dose. The results altogether suggest that the 224Ra‐labeled CaCO3 microparticles have promising properties for use as a localized internal α‐therapy of cavitary cancers.

Treatment of mice with NHL xenografts with Lu-lilotomab synergistically increased tumour suppression of subsequent anti-CD20 immunotherapy and improved survival. If the same effect is confirmed in a recently started clinical study, it could change the way radioimmunotherapy and CD20 immunotherapy would be used in the future.

Background: Patients with NHL who are treated with rituximab may develop resistant-disease, often associated with changes in expression of CD20. The next generation -particle emitting radioimmunoconjugate 177 Lu-lilotomab-satetraxetan (Betalutin ®) was shown to up-regulate CD20 expression in different rituximab-sensitive NHL cell lines and to act synergistically with rituximab in a rituximab-sensitive NHL animal model. We hypothesized that 177 Lu-lilotomabsatetraxetan may be used to reverse rituximab-resistance in NHL. Methods: The rituximab-resistant Raji2R and the parental Raji cell lines were used. CD20 expression was measured by flow cytometry. ADCC was measured by a bioluminescence reporter assay. The efficacies of combined treatments with 177 Lu-lilotomab-satetraxetan (150MBq/kg or 350MBq/kg) and rituximab (4×10mg/kg) were compared with those of single agents or saline in a Raji2R-xenograft model. Cox-regression and the Bliss independence model were used to assess synergism. Results: Rituximab-binding in Raji2R cells was 36±5% of that in the rituximab-sensitive Raji cells. 177 Lu-lilotomab-satetraxetan treatment of Raji2R cells increased the binding to 53±3% of the parental cell line. Rituximab ADCC-induction in Raji2R cells was 20±2% of that induced in Raji cells, while treatment with 177 Lu-lilotomab-satetraxetan increased the ADCC-induction to 30±3% of Raji cells, representing a 50% increase (p<0.05). The combination of rituximab with 350MBq/kg 177 Lu-lilotomab-satetraxetan synergistically suppressed Raji2R tumor growth in athymic Foxn1 nu mice. Conclusion: 177 Lu-lilotomab-satetraxetan has the potential to reverse rituximab-resistance; it can increase rituximab-binding and ADCC-activity in-vitro and can synergistically improve antitumor efficacy in-vivo.