Basic Science Investigation
ImmunoPET studies of 64Cu-labeled CD30 monoclonal antibody 64Cu-NOTA-CD30 in lymphoma models
Yang Xu, Li Cuicui, Liu Jun, Zhang Mingyu, Gong Jianhua, Miao Qingfang, Yang Jigang
Published 2023-03-25
Cite as Chin J Nucl Med Mol Imaging, 2023, 43(3): 171-176. DOI: 10.3760/cma.j.cn321828-20220131-00030
Abstract
ObjectiveTo develop the anti-CD30 monoclonal antibody 64Cu-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD30 and visualize CD30 expression in lymphoma non-invasively.
MethodsThe CD30 expression levels of 5 cell lines (Karpas299, Raji, Daudi, Ramos, and U266) were assessed by Western blot. Cell lines with high and low CD30 expression were selected for flow cytometry to evaluate the specific binding affinity of anti-CD30 monoclonal antibody. Thirteen NSG mice were used to established CD30 positive and negative subcutaneous xenograft models. 64Cu-NOTA-CD30 was obtained and 64Cu-NOTA-immunoglobulin (Ig)G was used as the control. ImmunoPET imaging was performed 2, 24, and 48 h after the injection of 64Cu-NOTA-CD30 or 64Cu-NOTA-IgG. Finally, the biodistribution studies were conducted. Repeated-measures analysis of variance and Bonferroni test were conducted for comparison.
ResultsKarpas299 showed the highest CD30 expression, while Raji showed the lowest. Flow cytometry showed specific binding affinity of the anti-CD30 monoclonal antibody to the Karpas299 cell line. The radiochemical purities of the probes were both higher than 95%. In microPET, the 64Cu-NOTA-CD30 uptake of Karpas299 xenograft tumors increased over time, with (11.46±0.58), (17.60±1.16) and (19.46±0.99) percentage activity of injection dose per gram of tissue (%ID/g) at 2, 24 and 48 h respectively. The contrast to normal tissue was good at 48 h, with the tumor/heart (blood) ratio of 2.20±0.22. The uptake of 64Cu-NOTA-CD30 in Karpas299 tumor at 48 h after injection was significantly higher than that in Raji tumor ((6.10±1.03) %ID/g) and 64Cu-NOTA-IgG in Karpas299 tumor ((5.12±0.89) %ID/g; F=290.99, t values: 19.65 and 22.25, all P<0.001). The uptake of 64Cu-NOTA-CD30 and the control probe in the heart and liver decreased over time in all groups. Ex vivo biodistribution at 48 h was mainly consistent with the results of microPET in vivo.
Conclusions64Cu-NOTA-CD30 is able to visualize the expression level and distribution of CD30 non-invasively. It is promising to be applied for screening the beneficial groups and evaluating efficacy for CD30-targeted immunotherapy.
Key words:
Lymphoma; Antibodies, monoclonal; Antigens, CD30; Isotope labeling; Copper radioisotopes; Positron-emission tomography; Tumor cells, cultured; Mice
Contributor Information
Yang Xu
Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Li Cuicui
Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Liu Jun
Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Zhang Mingyu
Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Gong Jianhua
Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Miao Qingfang
Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Yang Jigang
Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
