Preclinical evaluation of 89Zr labeled Daratumumab for imaging diagnosis of multiple myeloma
10.3760/cma.j.cn321828-20211116-00404
- VernacularTitle:89Zr标记达雷妥尤单克隆抗体用于多发性骨髓瘤显像诊断的临床前评价
- Author:
Haitao ZHAO
1
;
Lianghua LI
;
Weijun WEI
;
Yumei CHEN
;
Chun LYU
;
Cheng WANG
;
Jianjun LIU
Author Information
1. 上海交通大学医学院附属仁济医院核医学科，上海 200127
- Keywords:
Antibodies, monoclonal;
Antigens, CD38;
Isotope labeling;
Zirconium;
Positron-emission tomography;
Multiple myeloma;
Mice;
Rabbits
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2022;42(2):68-73
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To prepare 89Zr labeled Daratumumab and evaluate its feasibility in the imaging diagnosis of multiple myeloma (MM). Methods:According to the principle of 89Y (p, n) 89Zr nuclear reaction, 89Zr was produced by cyclotron solid target system (30 μA, 1.5 h) and automatic purification module. The radionuclide purity, half-life and impurity metal ion concentration were detected. Desferrioxamine (DFO) was coupled with Daratumumab and then chelated with 89Zr to prepare 89Zr-DFO-Daratumumab. The quality control analyses of three consecutive batches were carried out. Pharmacokinetic evaluation and 89Zr-DFO-Daratumumab microPET/CT imaging were performed in normal rabbits and orthotopic myeloma mouse models, respectively. The SUV in situ myeloma and that in normal bone were compared by independent-sample t test. Results:About 560 MBq of 89Zr was obtained, and there were only two characteristic energy peaks of 89Zr (909 keV and 511 keV) by γ spectrometer. The half-life of 89Zr was 78.2 h, and the content of metal impurities was small. 89Zr-DFO-Daratumumab was prepared with pH of 7.2, radiochemical purity of more than 99%, good stability in vitro, and sterility and endotoxin tests were passed. Pharmacokinetic studies in rabbits showed that 89Zr-DFO-Daratumumab was gradually distributed from blood to liver, spleen, kidney and bone joints over time and metabolism. The results of microPET/CT imaging in orthotopic myeloma mouse models showed that the SUVs of 89Zr-DFO-daratumumab in situ myeloma were significantly higher than those in normal bone (2 h: 0.22±0.02 vs 0.06±0.00; 1 d: 0.38±0.01 vs 0.08±0.00; t values: 8.89, 21.90, both P=0.001). Conclusion:89Zr and 89Zr-DFO-daratumumab are successfully prepared, and relevant quality control and biological evaluation in vivo and in vitro are completed, which verify the feasibility of 89Zr-DFO-Daratumumab in the imaging diagnosis of MM, thus laying a foundation for clinical transformation.
