Nuklearmedizin 2019; 58(02): 136
DOI: 10.1055/s-0039-1683563
Vorträge
Radiochemie und -pharmazie
Georg Thieme Verlag KG Stuttgart · New York

A Novel Tracer for GD2-Positive Neuroblastoma

S Spreckelmeyer
1   Charité Berlin, Nuclear Medicine Department, Berlin
,
J Rogasch
1   Charité Berlin, Nuclear Medicine Department, Berlin
,
K Schönbeck
2   Charité Berlin, Pediatric Hematology and Oncology, Berlin
,
N Beindorff
3   Charité Berlin, Experimental Radionuclide Imaging, Berlin
,
HN Lode
4   University Hospital Greifswald, Pediatric Hematology and Oncology, Greifswald
,
J Schulte
2   Charité Berlin, Pediatric Hematology and Oncology, Berlin
,
P Hundsdörfer
2   Charité Berlin, Pediatric Hematology and Oncology, Berlin
,
H Amthauer
1   Charité Berlin, Nuclear Medicine Department, Berlin
› Author Affiliations
Further Information

Publication History

Publication Date:
27 March 2019 (online)

Also available at
 
 

    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.


    #