18A. Diagnostic radiopharmaceuticals for neuroblastoma tumors

Immunotherapy revolutionized cancer therapy for adults, but successes have not been translated to the pediatric population as most checkpoint inhibitors do not seem to have the same potential in the pediatric population. Exceptions are GD2 and B7-H3, which are validated as immunotherapeutic targets in high risk neuroblastoma. B7-H3 also shows potential in other pediatric solid tumours and even has high interest from the adult oncological field

Monoclonal antibodies (mAbs) against GD2 and B7-H3 s are dinutuximab beta (anti-GD2), that is incorporated in the standard treatment in high risk neuroblastoma,  enoblituzumab and omburtamab (both anti-B7-H3) which are under clinical development. For GD2 expresion, neuroblastoma tumors are in 90-95% positive using immunohistochemistry (IHC). However, an increased survival rate is reported of only 46 to 66% for patients. To date it cannot be predicted which patients will benefit from dinutuximab immunotherapy.

Nuclear imaging of Zirconium-89 (⁸⁹Zr) labeled mAbs are successful as ImmunoPET tracers to visualize its distribution in vivo, study disease biology and predict therapeutic outcome in adults. Its potential is however unexplored in the pediatric population, let alone in neuroblastoma.

Aim: To develop ImmunoPET tracers to visualize GD2 and B7-H3 expression of neuroblastomas in vivo, hopefully aiding  assessment of treatment sensitivity and personalization of therapy in the future.

Plan of investigation: ImmunoPET tracers against GD2 and B7-H3, being [⁸⁹Zr]dinutuximab, [⁸⁹Zr]enoblituzumab,  [⁸⁹Zr]omburtamab will be developed for molecular imaging of their respective targets. Their potential will be assessed in preclinical studies on neuroblastoma tissue cultures and in neuroblastoma mouse models from the Princess Maxima Biobank. Though foreseen, clinical translation of [⁸⁹Zr]dinutuximab to image GD2 positive neuroblastoma patients is not part of this project.

Expected results: The ability for in vivo visualization of GD2 and B7-H3 expression levels. We expect to correlate the tracer accumulation to target expression in preclinical studies. This will be a big step towards personalized immunotherapy for pediatric oncological patients in the future.

Necessary skills for this position:

• Medical degree