NB MRD RIT & RID

499 Objectives The prognosis for patients with metastatic neuroblastoma (NB) is poor, primarily because micrometastases survive initial therapy and this minimal residual disease (MRD) returns in the form of wide-spread tumors. There is, therefore, a need for more effective NB treatment in the MRD setting. The goal of this study was to evaluate the efficacy of 177Lu radioimmunotherapy (RIT) for the treatment of MRD in NB. Methods An intraheptic model of MRD was established by the injection of human NB cells (IMR32) into nude mice. After 2 weeks of tumor growth, animals were treated with 177Lu-labeled hu14.18K322A, an anti-GD2 antibody, in two doses, either 1.3 or 5.9 MBq, and imaged with 89Zr-labeled hu14.18K322A at 2 and 4 weeks post-treatment to monitor tumor growth. Results In this orthotopic model, RIT was effective, significantly extending survival of the low-dose group to a mean of 74.5 days and of the high-dose group to a mean of 73 days compared with controls (mean of 49 days, log rank analysis (Mantel-Cox) p=0.015). The results of the 89Zr-hu14.18K322A radioimmunodetection (RID) studies correlated with survival. For example, at 2 weeks post-therapy, PET images of control and treated animals were similar, but by 4 weeks liver metastases were observed in the control mice but not in the treated animals. Ex vivo biodistribution and autoradiography confirmed high uptake of radiolabeled antibody in sub-millimeter tumors compared with surrounding liver with tumor-to-liver count ratios of 10-20:1. Conclusions These data suggest that 177Lu-labeled hu14.18K322A may be effective for use in RIT treatment of MRD in NB and that 89Zr-labeled hu14.18K322A may be effective for monitoring therapeutic response to RIT treatment of MRD in NB.