Demonstration of a Correlation between Tumor Absorbed Dose and Response in Several Pediatric Tumor Xenografts Treated with Radioiodinated CLR1404 Alkyl-Phospholipid Ether

Radionuclide therapy combines the specificity of cancer cell targeting with the well-known cytotoxic effects of ionizing radiation. It has the potential to simultaneously eradicate both the primary tumor site as well as the metastatic extent of the disease throughout the body. Radionuclide therapy in the form of ¹³¹Imetaiodobenzylguanidine (¹³¹I-MIBG) has been used for several years to treat pediatric patients with advanced forms of neuroblastoma. ¹³¹I-MIBG treatments have improved palliation and progression-free survival rates in predominantly relapsed and refractory patients who have already endured an extensive chemotherapy regimen. MIBG is selectively taken up by an active transport mechanism in only neuroblastoma cells, limiting its applicability to other pediatric cancer types and additional radionuclide therapy options are needed. Several preclinical and clinical trials have shown selective in vitro uptake of ¹³¹I-CLR1404 in pediatric cancer cell lines. The focus of this work was to perform mouse-specific Monte Carlo-based dosimetry in several pediatric cancer xenografts being treated with ¹³¹I-CLR1404. Mouse-specific Monte Carlo-based dosimetry in radionuclide therapy can offer additional insight on the efficacy of new radiopharmaceuticals in organs and tumor volumes. In addition, this work demonstrates a clear dose-response relationship in these models