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

Area of Science:

• Nuclear medicine
• Immunotherapy
• Oncology

Background:

• Disialoganglioside GD2 antibodies are key in neuroblastoma immunotherapy.
• Radiolabeled antibodies offer potential for radioimmunotherapy and theranostic applications.
• Optimizing radiolabeling for antibody binding is crucial for targeted treatments.

Purpose of the Study:

• To investigate the impact of radiolabeling on ch14.18 antibody binding characteristics.
• To evaluate the utility of GD2-ImmunoPET for neuroblastoma therapy planning.
• To assess the theranostic potential of copper-64 labeled ch14.18/CHO antibodies.

Main Methods:

• Copper-64 (⁶⁴Cu) labeling of ch14.18 antibodies using NOTA or DOTAGA chelators.
• In vitro characterization of radiolabeled antibodies for purity, activity, and immunoreactivity.
• In vivo studies in a neuroblastoma mouse model using PET/MR imaging.
• Clinical PET/MR imaging in a patient with metastasized neuroblastoma.

Main Results:

• Radiolabeling achieved high purity (≥90%) and stability over 48 hours.
• Immunoreactivity of radiolabeled conjugates was maintained (50.8 ± 3.5%).
• Preclinical studies showed specific accumulation in neuroblastoma xenografts (31.6 ± 5.8% ID/g).
• Clinical PET/MR successfully visualized neuroblastoma metastases.

Conclusions:

• ⁶⁴Cu-labeled ch14.18/CHO antibodies are effective for specific neuroblastoma detection via PET.
• The developed GD2-ImmunoPET method shows clinical translation feasibility.
• This theranostic approach holds potential for image-guided neuroblastoma therapy planning.