Translational immunoPET imaging using a radiolabeled GD2-specific antibody in neuroblastoma

Background: Antibodies targeting surface expressed disialoganglioside GD2 are increasingly used in neuroblastoma immunotherapy and might also have potential for use in radioimmunotherapy. As such targeted treatments might benefit from a dedicated theranostic approach, we studied the influence of radiolabeling on the binding characteristics of ch14.18 antibodies produced by Chinese hamster ovary (CHO) cells and evaluated the benefit of GD2 ImmunoPET as a potential tool for therapy planning. Methods: Cu-64 was used to reduce radiation burden, which is of high importance especially in a pediatric patient population. Cu-64-labeling was accomplished using the chelators NOTA- or DOTAGA-NCS. Radiolabeled antibodies were characterized in vitro. [Cu-64]Cu-DOTAGA-ch14.18/CHO was studied in a neuroblastoma mouse model (subcutaneous CHP-134 xenografts). In vivo PET and MR images were acquired at 3 h, 24 h, and 48 h p.i. The specificity of binding was verified using GD2-negative tumors (HEK-293 xenografts), a control antibody and in vivo blocking. A first translational application was performed by PET/MRI in a patient with metastasized neuroblastoma. Results: Radiolabeling at an antibody-to-chelator ratio >= 1:10 yielded a product with a radiochemical purity of >= 90% and a specific activity of 0.2-1.0 MBq/mu g. Radiochelation was stable over 48 h in PBS, mouse serum or EDTA, and 50.8 +/- 3.5% and 50.8 +/- 2.0% of the radiolabeled conjugates, prepared at antibody-to-chelator ratios of 1:10 or 1:15, were immunoreactive. In vivo, highly specific accumulation (31.6 +/- 5.8% ID/g) in neuroblastoma was shown preclinically. Clinical PET/MR scans using [Cu-64]Cu-NOTA-ch14.18/CHO (NOTA used for safety reasons) could visualize neuroblastoma metastases. Conclusions: In vivo, Cu-64-labeled ch14.18/CHO is suitable for specific identification of neuroblastoma in PET. A first patient PET indicated the feasibility of the method for clinical translation and the potential utility in image-guided therapy.