GD2-targeted theranostics of neuroblastoma with [⁶⁴Cu]Cu/[¹⁷⁷Lu]Lu-hu3F8.

Abstract

Neuroblastoma (NB) is a malignant embryonic tumour with poor prognosis and high mortality rate. The antigen gisialoganglioside (GD2), which is highly expressed on the surface of NB cells, is an effective target for therapy. This study aims to evaluate the GD2 expression with [⁶⁴Cu]Cu-NOTA-hu3F8 positron emission tomography (PET) imaging and explore the radioimmunotherapy (RIT) effect of [¹⁷⁷Lu]Lu-DOTA-hu3F8 in NB tumour models. The in vitro validation of the binding ability of anti-GD2 humanised monoclonal antibody (hu3F8) to GD2 was achieved via flow cytometry, cell immunofluorescence, and cell uptake test. Hu3F8 were conjugated with p-SCN-Bn-NOTA (NOTA) and p-SCN-Bn-DOTA (DOTA) for ⁶⁴Cu- and ¹⁷⁷Lu- radiolabelling. PET imaging and RIT studies were conducted using [⁶⁴Cu]Cu-NOTA-hu3F8 and [¹⁷⁷Lu]Lu-DOTA-hu3F8 in subcutaneous NB tumour models. The Institute for Medical Research-32 (IMR32) cell line exhibited a specific binding ability of hu3F8. PET imaging demonstrated a specific accumulation of [⁶⁴Cu]Cu-NOTA-hu3F8 in IMR32 tumour models, with a maximum tumour uptake of 23.73 ± 2.29%ID/g (n = 3) at 72 h post-injection (p.i.), outperforming other groups significantly (P < 0.001). The high dose [¹⁷⁷Lu]Lu-DOTA-hu3F8 group (11.1MBq) showed the most potent tumour suppression, with a standardised tumour volume of about 20.47 ± 6.32% at 30 days p.i., significantly smaller than other groups (n = 5, P < 0.05). This study demonstrated that ⁶⁴Cu-/¹⁷⁷Lu- labelled hu3F8 could noninvasively evaluate the GD2 expression and effectively inhibit tumour growth in NB tumour models. The excellent therapeutic efficacy of [¹⁷⁷Lu]Lu-DOTA-hu3F8 may be helpful for the clinical translation of this GD2-targeted theranostics approach in GD2-positive tumours.