A Novel Tracer for GD2-Positive Neuroblastoma

Ziel/Aim:

Neuroblastoma is a malignant tumour that develops from the sympathetic nervous system. 7 – 8% of all diagnosed malignant tumours in childhood are neuroblastoma. In Germany, 150 children per year get diagnosed with this disease. At initial presentation ultrasound, MRI as well as SPECT scans with ¹²³I-metaiodobenzylguanidine (mIBG) are used to establish the diagnosis. Unfortunately, 5% of the cases are mIBG negative. However, nearly 100% of neuroblastoma patients express disialoganglioside GD2. Our goal was to synthesize bifunctional tracers that consist of a GD2 targeting vector. Furthermore, we aim to perform in vitro and in vivo experiments in order to elucidate their mechanism of action.

Methodik/Methods:

The radiotracers were synthesized using established protocols.(1) The logP values were assessed using the octanol/PBS coefficient. Human serum stability experiments were carried out at 37 °C. Radiochemical yields were calculated using iTLC. For the CAM assay, IMR-2 cells were used and analyzed with PET/MRI.

Ergebnisse/Results:

Two radiotracers (DOTA-Dinutuximab beta and DTPA-Dinutuximab beta) were successfully synthesized and radiolabelled with Gallium-68 and Lutetium-177 for imaging or therapeutic purposes, respectively. Both tracers show labeling efficiencies of > 90% with a marked stability in human serum in vitro. IMR-2 cells were used in a CAM assay in vivo to prove the functionality of our tracer. Concerning the affinity studies, we show significant differences between experiments performed at 37 °C vs. 4 °C.

Schlussfolgerungen/Conclusions:

To conclude, two bifunctional chelators were successfully linked to dinutuximab beta and they show promising radiolabeling properties – Ga-68 for immunoPET imaging and Lu-177 to combine immunological and radiobiological toxicity. Our preliminary results in vitro and in vivo are the basis for the planned in vivo experiments with GD2-positive tumor bearing mice.

Literatur/References:

[1] Spreckelmeyer, S.; Ramogida, C.F.; Rousseau, J.; Arane, K., et. al., Bionconj. Chem. 2017, 28, 2145 – 2159.