Experimental study of 89Zr-labeled anti-human PDPN monoclonal antibody SZ168 for immunoPET imaging of melanoma
10.3760/cma.j.cn321828-20240725-00273
- VernacularTitle:89Zr标记抗人PDPN单抗SZ168用于黑色素瘤免疫PET显像的实验研究
- Author:
Yu LIU
1
;
Xiaohui SUN
;
Siwen LIU
;
Jiang WU
;
Yue LANG
;
Jinchang WU
;
Yuechao YU
;
Yiming ZHAO
;
Feng WANG
Author Information
1. 徐州医科大学第二附属医院核医学科，徐州 221000
- Publication Type:Journal Article
- Keywords:
Antibody, monoclonal;
Antigen, PDPN;
Isotope labeling;
Zirconium-89;
Positron emission computed tomography;
Malignant melanoma;
Mouse
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2025;45(8):470-474
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To prepare 89Zr-labeled anti-human podoplanin (PDPN) monoclonal antibody SZ168 and evaluate its feasibility for melanoma immunoPET imaging. Methods:89Zr-desferrioxamine (DFO)-SZ168 was prepared by conjugating p-isothiocyanatobenzyl (SCN-Bn)-DFO with SZ168 and chelating with 89Zr. Quality control analyses were conducted, including labeling rate, radiochemical purity, and in vitro stability. Melanoma mouse models were created, with experimental group ( n=3) and control group ( n=3) receiving tail vein injections of 89Zr-DFO-SZ168 and 89Zr-DFO-immunoglobulin (Ig)G solutions (3.7MBq) respectively. The experimental group underwent microPET/CT imaging at 12, 24, 48 and 72h post-injection, while the control group underwent imaging at 48h post-injection. Tumor and organ radioactivity uptake was analyzed using the ROI method. Mice were sacrificed at 7d post-injection to assess the ex vivo biodistribution of 89Zr-DFO-SZ168 and 89Zr-DFO-IgG. Independent-sample t test was used to analyze the data. Results:The pH value of the 89Zr-DFO-SZ168 solution was approximately 7.0, with a labeling rate >60%, radiochemical purity >95% after PD10 column purification, and good stability after 72h in vitro. Series microPET/CT imagings showed significant tumor visualization in tumor-bearing mice. Radioactivity uptake in tumors peaked at 48h post-injection, while the tumor was not clearly detected by 89Zr-DFO-IgG microPET/CT imaging. Ex vivo biodistribution indicated that 89Zr-DFO-SZ168 mainly accumulated in tumors, liver, and bones, with tumor uptake significantly higher than that of 89Zr-DFO-IgG ((29.36±7.29) percentage activity of injection dose per gram of tissue (%ID/g) vs (8.78±1.63) %ID/g; t=4.77, P=0.009). Immunohistochemistry of tumor specimens showed high expression of PDPN in tumor tissues. Conclusions:The probe 89Zr-DFO-SZ168 is successfully prepared, showing potential for specific molecular imaging diagnosis of melanoma. This lays a basis for developing PDPN molecular target-based immuno-PET diagnosis and integrated diagnosis and treatment for melanoma.
