Preclinical evaluation of 64Cu/177Lu-labelled anti-CD30 monoclonal antibody for theranostics in CD30-positive lymphoma

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Abstract
Purpose CD30 serves as an ideal therapeutic target for lymphoma, but its variable expression and high relapse rate pose challenges in targeted therapy. This study aims to label the anti-CD30 monoclonal antibody with 64Cu/177Lu for immuno-positron emission tomography (immuno-PET) and radioimmunotherapy (RIT). Methods CD30 binding kinetics of anti-CD30-IgG (IMB16) were measured by Biolayer interferometry (BLI). Western blotting screened lymphoma cell lines for CD30 expression. Flow cytometry and immunofluorescence validated the specific binding of IMB16. IMB16 was conjugated to p-SCN-Bn-NOTA(NOTA) and p-SCN-Bn-DOTA(DOTA) for radiolabeling with 64Cu and 177Lu. [64Cu]Cu-NOTA-IMB16 and [177Lu]Lu-DOTA-IMB16 were used for immuno-PET and RIT in subcutaneous lymphoma NSG mouse models. Results IMB16 had a strong binding affinity to CD30 according to the BLI. Western blotting revealed high CD30 expression in Karpas299 cells and negative expression in Raji cells. Flow cytometry and immunofluorescence confirmed specific binding of IMB16 to CD30 on cell surface. Radiochemical purity of [64Cu]Cu-NOTA-IMB16 and [177Lu]Lu-DOTA-IMB16 exceeded 95%. In Immuno-PET imaging, CD30-positive Karpas299 tumours had a mean uptake value of 19.2 ± 0.9%ID/g (n = 3) at 24 h post-injection, significantly higher than Karpas299-blocked and Raji-negative groups (P < 0.001). A high radiation dose (300µCi) of [177Lu]Lu-DOTA-IMB16 significantly inhibited tumour growth (80.2 ± 17.6% standardized tumour volume, n = 5) at 10 days post-injection, compared to controls. Ex vivo biodistribution and histological staining supported in vivo PET imaging and RIT results. Conclusions Labelling IMB16 with 64Cu enabled non-invasive assessment of CD30 expression, while 177Lu labelling effectively suppressed tumour growth in CD30-positive lymphoma. CD30-targeted theranostic show promise for patient stratification and treatment enhancement, warranting further clinical evaluation.
Funding Information
  • National Natural Science Foundation of China (82202206, 82272034, 82302235)
  • Beijing Natural Science Foundation (7234359)
  • Beijing Postdoctoral Research Foundation (364329)
  • China National Postdoctoral Program (GZC20231753)
  • Beijing Friendship Hospital Seed Project of Capital Medical University (YYZZ202338)

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